Articles

Child Health Management using Probiotics

Rashmi Goley¹, Amar P. Garg^2*
1School of Biotechnology & Life Sciences, Shobhit Institute of Engineering & Technology, Modipuram, NH-58, Meerut- 250110, India.
²Swami Vivekanand Subharti University, NH-58, Subhartipuram, Meerut-250005 India.

Article Info

Received Date: 05 March 2025, Accepted Date: 01 April 2025, Published Date: 02 April 2025

*Corresponding author: Amar P. Garg, Swami Vivekanand Subharti University, NH-58, Subhartipuram, Meerut-250005 India.

Citation: Rashmi Goley, Amar P. Garg. (2025). Child Health Management using Probiotics. Journal of International Pediatrics and Child Health, 1(1); DOI: http;/04.2025/JIPCH/002.

Copyright: © 2025 Amar P. Garg. This is an open-access article distributed under the terms of the Creative Commons Attribution 4. 0 international License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The increasing interest in probiotics for childrens health has led to a growing body of research exploring their potential benefits in promoting overall well-being. Probiotics, defined as live microorganisms that offer health benefits when consumed in adequate amounts, are commonly used to support gastrointestinal health, boost immune function, and prevent or alleviate common childhood ailments such as diarrhoea, constipation, and colic. This paper provides a comprehensive review of the current evidence on the safety, efficacy, and benefits of probiotic supplementation in paediatric populations. It evaluates various forms of probiotics, including powders, gummies, liquids, and drops, highlighting their effectiveness in maintaining gut microbiota balance and enhancing digestive health. The paper further explores the role of specific probiotic strains, such as Lactobacillus and Bifidobacterium, and their impact on childrens health outcomes. Additionally, the paper examines critical factors such as appropriate dosages, strain selection, and age-specific formulations to ensure optimal use of probiotics in children. While the benefits of probiotics for digestive and immune health in children are well-supported, concerns regarding the potential for adverse effects, proper storage, and long-term safety are also addressed. The paper concludes by providing evidence-based recommendations for parents, caregivers, and healthcare professionals on the safe and effective use of probiotics in paediatric care, emphasizing the need for further research to better understand their role in childrens health and development.

Keywords: probiotics; child health management; lactic acid bacteria; prebiotics; gastic infections; respiratory diseases

Introduction

The gut microbiota is essential to general health during childhood, a time of fast growth and development. Immune development, metabolism, nutrition absorption, and pathogen defence are all aided by a healthy gut flora. Gastrointestinal disorders, allergies, and compromised immune responses are just a few of the health problems that can result from disruptions brought on by things like drugs, inadequate diet, or infections [1]. According to recent studies, probiotics—live microorganisms with health benefits—may alter the gut microbiota and enhance the health of children. They are a fascinating field of study for advancing the health of children because of this.

The term "probiotic" was defined in 2001 by an Expert Panel of the Food and Agricultural Organization of the United Nations (FAO) and the World Health Organization (WHO) [2]. In 2013, the International Scientific Association for Probiotics and Prebiotics (ISAPP) reviewed the field of probiotics and literature, and reiterated the definition as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” This definition is widely accepted in the scientific community. Increased knowledge of probiotics benefits has led to an exponential growth in commercial products [3]. However, safety concerns are raised since many are categorised as dietary supplements, which frequently go through less severe requirements and quality control than pharmaceutical goods. It has been proposed that probiotics may transmit genes that code for antibiotic resistance, and there have been case reports of probiotics stimulating the immune system and causing systemic infections in vulnerable groups [4]. Despite this, there is strong evidence that probiotics are safe for the general public, and side effects are uncommon and mostly restricted to high-risk groups [5]. Lactic acid-producing species such Lactobacillus and Bifidobacterium, as well as Streptococcus, Enterococcus, Lactococcus, Pediococcus, Bacillus, Escherichia, and Saccharomyces, are among the frequently utilised probiotics. Variation in studies, including strain heterogeneity, dosage, matrix, administration route, and research protocols, has limited consensus on probiotic use (Different organizations, including the American Gastroenterology Association (AGA), the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) [6}, and the American Academy of Paediatrics (AAP), have published differing evidence-based recommendations, particularly regarding necrotizing enterocolitis [7,8]. Evidence-based guidelines for the use of probiotics in children require more investigation and well planned studies. Probiotic efficacy varies depending on the strain and illness, and it is also influenced by the matrix in which it is taken. When prescription probiotics, medical professionals should take both aspects into account [9].

The composition and activity of gut microbiota are closely linked to human health. Changes in gut microbiota, or dysbiosis, have been linked to neurological and behavioural problems, metabolic syndrome, inflammatory, allergy, and autoimmune illnesses, as well as functional gastrointestinal disorders. The perinatal period and early life are critical for establishing a healthy microbiota, which influences immune and metabolic responses [10]. Disruptions during this period can have long-term health implications. Lachnospiraceae and Clostridium are more prevalent in full-term infants with moderate hypoxia, and they are associated with impaired brain development and communicative abilities at six months [11]. Preterm neonates often experience dysregulated microbiota due to factors like C-section, medications, and reduced breastfeeding. The use of probiotics, such as Bifidobacterium longum subsp. infantis (B. infantis) EVC001, in preterm neonates has shown promise in increasing beneficial intestinal bacteria, reducing inflammation, and combating antibiotic resistance. In paediatric intensive care units, children with sepsis often experience an overgrowth of pathogenic bacteria and a reduction in beneficial commensal bacteria, leading to dysbiosis [12]. Whether dysbiosis causes or results from severe infections is still unclear. Strategies to promote healthy gut microbiota, including probiotics like bovine lactoferrin and Lactobacillus rhamnosus GG (LGG), have shown mixed results in preventing conditions like late-onset sepsis and antibiotic-associated diarrhoea. The richness of gut microbiota, with a relative abundance of Firmicutes and Bacteroidetes, specifically the genera Alistipes and Subdoligranulum, which produce propionate and butyrate, was found to be negatively correlated with body mass index (BMI) during childhood in a recent study involving 160 healthy children aged 0–12 [13]. Numerous environmental and nutritional variables might affect gut microbiota, which is thought to be a treatment target for possible allergies [14,15]

By controlling intestinal and systemic immunity and re-establishing intestinal permeability, Lactobacillus rhamnosus GG (LGG) has been used to prevent atopy and increase tolerance to cows milk protein in children with allergies. Tan et al.s comprehensive review and meta-analysis showed that LGG was safe and effective for children with cows milk allergies under the age of three [16]. LGG reduced faecal occult blood but showed no significant difference in dermatitis scores. Even in the absence of underlying anatomical and biochemical problems, functional gastrointestinal disorders—which are frequently linked to dysbiosis—have been linked to pain management with LGG and other probiotic strains [17].

Studies have shown that microbiota influences the gut-brain axis, affecting the reaction to stress, inflammation and pain stimuli [18]. Numerous physiological processes, including as cytokine profiles, intestinal and blood-brain permeability, metabolism, and levels of neurotransmitters and neuroactive chemicals, may be modulated by targeted dietary therapies and specific probiotics. However, only a small number of randomised controlled trials have demonstrated minimal efficacy in lowering pain, and there is no conclusive evidence to support the use of probiotics for avoiding functional gastrointestinal diseases. Although the factors influencing this positive impact are yet unknown, one study found that L. reuteri DSM179389 considerably decreased the amount of time that breastfed babies spent crying and/or fussing. The comparison and interpretation of results are limited by the heterogeneity of research [20,21].

Probiotics and Prebiotics in Paediatrics:      

Probiotic: A dietary product or oral supplement that contains enough live microorganisms to change the microbiota of the host and maybe improve health. According to the Council for Agricultural Science and Technology (2010) [22], probiotics are fermentative, anaerobic bacteria that create lactic acid and have the ability to outcompete harmful microorganisms in the human gut. They are commonly found in the genera Lactobacillus, Bifidobacterium, and Streptococcus. Beneficial metabolic by products produced by these microorganisms, such butyrate and other short-chain fatty acids, have the ability to influence the immune system. Probiotic microorganisms such as Streptococcus thermophiles, Bifidobacterium lactis, and Lactobacillus rhamnosus GG (LGG) are often researched [23]. These are distinct from potentially dangerous bacteria that do not produce lactic acid, such as Proteus species, Pseudomonas, Serratia, and Klebsiella, which can spread across the intestinal epithelium and cause illness. Probiotics can also be made from yeasts like Saccharomyces boulardii. Probiotics are ingested as functional foods, medications, or supplements [24,25].

Prebiotic: An indigestible dietary component that helps the host by specifically promoting the development and/or activity of one or more naturally occurring probiotic microorganisms. According to Robertfroid [26], prebiotics are usually oligosaccharides that are either naturally occurring or given as dietary supplements to meals, drinks, and baby formula. Although they are indigestible by humans, they promote the colons growth of some probiotic bacteria, especially Bifidobacteria [27,28]. Prebiotic oligosaccharides are typically composed of 10 or fewer sugar molecules and frequently comprise fructose chains with a terminal glucose. Inulin, galacto-oligosaccharides (GOSs), soybean oligosaccharides, and fructo-oligosaccharides (FOSs) are a few examples. Several FOS molecules combine to form the composite oligosaccharide known as inulin [29,30]. Dietary fibres complex polysaccharides can also function as prebiotics. Although dietary nucleotides are not strictly prebiotics, they have prebiotic-like properties and can modulate the immune system and intestinal functions. While real milk includes a significant and fluctuating amount of oligosaccharides and free nucleotides, some baby formulae only contain a little amount of these substances. Prebiotic oligosaccharides are now being added to infant formula by manufacturers. Additionally, different levels of oligosaccharides and nucleotide additions are included in beverages and nutritional supplements for older babies, children, and adults [31].

Functional foods: Every altered food or food ingredient which offers health benefits above and beyond those attributed to any particular nutrient or nutrients it contains is referred to as a functional food. It must continue to be a meal and exhibit its effects at quantities typically expected to be ingested through diet. Functions related to enhancing health and well-being and/or lowering the risk of disease are examples of benefits. A food is considered functional if it includes probiotics or prebiotics. Live culture yoghurt that includes prebiotics, probiotic bacteria, and other nutritional elements is an example of a functional food. Since human milk has high concentrations of oligosaccharides, or prebiotics, and maybe some naturally occurring probiotic bacteria (one study showed 103 bifidobacteria per millilitre of expressed human milk), it can also be considered a functional food [33].

Synbiotic: A supplement that has both prebiotics and probiotics. There is no need for proof of a particular prebiotic and probiotic interaction. Synbiotics can be added to functional meals or used as stand-alone supplements.

Postbiotic: A probiotic microorganisms metabolic byproduct that alters the biological processes of the host.

Microbes are crucial for human health, and attempts to maximise intestinal microbiota led to heightened interest in probiotics and prebiotics. These supplements should be backed by evidence-based medicine. Human milk which is considered as natural prebiotic, is recommended for infants up to six months due to its substantial oligosaccharide content, promoting healthy microbiota. Probiotics can decrease the duration of acute viral gastroenteritis in children but are not routinely recommended to prevent infectious diarrhoea unless in special circumstances. They can help prevent antibiotic-associated diarrhoea but not treat it. While probiotics may benefit at-risk infants for atopic disorders, more evidence is needed for routine use recommendations. For preterm infants over 1000g, probiotics may help prevent necrotizing enterocolitis (NEC), but many questions remain about the specific probiotics to use. There is limited evidence for the long-term benefits of probiotics in treating disorders like Crohns disease, constipation and IBS in children (European Food Safety Authority Microorganisms in food and feed., 2010) [34]. Probiotics may help with H. pylori infections, chronic ulcerative colitis, and infantile colic, but more studies are required. The long-term benefits of probiotics in preventing diseases or providing sustained immune benefits are still unproven. Adding probiotics to infant formula is safe but deprives evidence of clinical efficacy for routine use. Probiotics should not be given to seriously ill children until their safety is confirmed. Prebiotics may reduce infections and atopy in healthy children, but further studies are needed. Adding oligosaccharides to infant formula is reasonable but lacks evidence of clinical efficacy, and cost/benefit studies are needed. Important questions remain regarding optimal probiotic administration duration, dose, species, and long-term impacts on childrens gut microflora. The benefits of probiotics during pregnancy and lactation versus those in infant formulas need further research, as do similar questions for prebiotics. This report guides paediatric healthcare providers in making informed decisions about probiotics and prebiotics for their patients [35].

Types of probiotics strains commonly used in children: 

Lactobacillus rhamnosus: It is a highly adaptable facultative anaerobic bacterium with a diverse genome, allowing it to utilize a broad range of carbohydrates like lactose, glucose, galactose, and fructose [36]. This metabolic flexibility facilitates L. rhamnosus to thrive in various environments within the gastrointestinal tract, promoting a balanced gut microbiome. The bacterium produces essential metabolites like acetic acid, lactic acid and short-chain fatty acids (SCFAs), including butyrate, which help maintain a low pH in the gut. This acidic environment restricts pathogenic bacteria and supports a healthy gut ecosystem. One of the unique features of L. rhamnosus is its ability to metabolize fucose through specialized pathways, generating metabolites such as lactic acid, acetic acid, 1,2-propanediol, formic acid, and carbon dioxide [37]. These molecules set L. rhamnosus apart from other lactic acid bacteria and are essential for bacterial growth and energy generation.

Additionally, it synthesizes antimicrobial peptides, including bacteriocins, which prevent the growth of harmful pathogens in the gut. This strain is also known for its production of extracellular polysaccharides (EPSs), which contribute to biofilm formation. The bacteriums capacity to stick to the gut surface and withstand environmental stresses such bile salts and low pH levels is improved by these EPSs [38]. Additionally, it generates antioxidant enzymes like glutathione reductase and superoxide dismutase (SOD), which shield the host cells and the bacteria from oxidative stress and promote gut health. L. rhamnosuss ability to interact with dendritic cells to stimulate the synthesis of anti-inflammatory cytokines like IL-10 is a significant immunomodulatory characteristic.

This immunoregulation supports its role in maintaining gut homeostasis and enhancing the immune response. Additionally, it secreates inosine, a metabolite with anti-inflammatory, antioxidant, anti-infective, and neuroprotective effects [39]. This production is higher in L. rhamnosus in comparison to other Lactobacillus species, highlighting its unique metabolic capabilities. Lactobacillus rhamnosus has been widely studied for its beneficial effects in clinical settings, especially in gastrointestinal health and immune modulation in children. It is often included in probiotic supplements to promote digestive health, prevent diarrhoea, and manage conditions like irritable bowel syndrome (IBS) and respiratory infections. Its capacity to enhance gut barrier integrity and support the immune system makes it an essential strain in paediatric probiotic formulations. In addition to its gastrointestinal benefits, recent research is exploring L. rhamnosus for its potential role in mental health, particularly in addressing stress, anxiety, and neuro inflammation. The strains ability to modulate the gut-brain axis suggests a promising avenue for future studies on probiotics as adjunct therapies in mental health management [40].

Bifidobacterium infantis: Specifically, the subspecies B. longum subsp. infantis, is uniquely adapted to thrive in the infant gut due to its specialized genomic features. These adaptations enable the metabolism of human milk oligosaccharides (HMOs), which are abundant in breast milk and serve as a primary carbohydrate source for infants [41]. B. infantis has an advantage in the intestinal environment of infants because its genome has a large number of genes that encode glycosyl hydrolases and transport proteins that particularly target and degrade HMOs [42]. This unique metabolic capability helps B. infantis establish itself in the infants digestive system, where other bacteria may struggle. In addition to its ability to utilize HMOs, B. infantis secretes essential metabolites like acetate and lactate. These short-chain fatty acids (SCFAs) play important role in supporting gut health by strengthening the intestinal barrier and enhancing tight junction integrity, which prevents the translocation of harmful pathogens. The bacterium also produces various other SCFAs, which provide energy for colonocytes and contribute to maintaining overall gut homeostasis. One of the interesting aspects of B. infantis is its ability to produce indole-3-lactic acid (ILA), despite not having direct genetic pathways for its synthesis [43,44]. This metabolite results from B. infantiss ability to metabolize tryptophan, particularly when it is cultured with HMOs. ILA has been associated with beneficial effects on gut health, including modulating the gut microbiota and supporting immune function. Moreover, B. infantis stands out among Bifidobacterium species due to its numerous bacteriocin gene clusters, including lanthipeptides and thiopeptides [45]. These antimicrobial peptides allow B. infantis to inhibit the growth of harmful microorganisms, providing a competitive edge in colonizing the infant gut and helping to maintain a balanced microbiome. In addition to its gastrointestinal advantages, B. infantis has been demonstrated to create the metabolite inosine, which has cardioprotective properties. Specifically, by activating the adenosine A2A receptor, inosine reduces myocardial inflammation and cell death after ischemia/reperfusion damage [46].

This activation reduces pro-inflammatory cytokines and promotes ATP production through the purine salvage pathway, suggesting that B. infantis may have broader therapeutic potential beyond gut health. Overall, Bifidobacterium infantis plays a vital role in early infant development, supporting gastrointestinal health, immune function, and potentially even heart health, through its unique metabolic activities and production of beneficial metabolites [47,48]. A well-known probiotic bacterium that is frequently present in fermented dairy products, Streptococcus thermophilus, is essential for supporting gut health and affecting host metabolism. Lactate, which is generated by the glycolysis process, is one of its main metabolites [49]. Lactate decreases the pH in the stomach, which affects the colon epithelium and helps milk coagulate during fermentation. This alteration can have a beneficial impact on gut health and function by influencing the expression of several transporters and proteins involved in cell cycle control. Leucine, isoleucine, proline, aspartic acid, and tryptophan are among the amino acids that S. thermophilus generates in addition to lactate [50].

These amino acids have a major impact on the quality and sensory qualities of fermented dairy products and are necessary for the bacteriums development [51]. The flavour profile and general features of the fermentation process are influenced by the fatty acids and metabolites that the strain generates, such as 2-hydroxybutyric acid, D-Glycerol-D-galactose-heptanol, and hydra starch [52]. Numerous amino acids, including as cysteine, methionine, glutamate, glutamine, arginine, aspartate, asparagine, and alanine, are broken down and used in S. thermophilus metabolic pathways. These amino acids are crucial for synthesizing glutathione, a powerful antioxidant that helps the bacterium cope with oxidative stress and environmental challenges, ensuring its survival in harsh conditions. Beyond its metabolic impact, S. thermophilus also plays a role in modifying tryptophan metabolism, which can result in reduced levels of indole derivatives and increased serotonin production. This shift in metabolism has broader implications for gut-brain interactions and mood regulation, suggesting that S. thermophilus may have a role in mental well-being. Additionally, S. thermophilus produces bacteriocins, which are antibiotic-like compounds with bactericidal properties. These bacteriocins help reduce uremia and inhibit the growth of pathogenic microbes, reinforcing its probiotic benefits and making it a valuable tool for maintaining gut health and preventing infections caused by harmful bacteria. Overall, the metabolic versatility and probiotic properties of S. thermophilus highlight its significance not only in the dairy industry but also in enhancing gastrointestinal health and potentially influencing broader health outcomes [53].

Lactobacillus acidophilus: This renowned probiotic bacterium is known to produce a number of metabolites that support gut health, including as bacteriocins (BACs), exopolysaccharides (EPSs), and conjugated linoleic acid (CLA). A number of variables, including pH, temperature, incubation duration, yeast extract content, and the availability of free linoleic acid, affect the synthesis of these metabolites [54.55].  These metabolites contribute to the bacteriums ability to support a healthy gut microbiota and provide additional health benefits. Bacteriocins, antimicrobial peptides secreted by L. acidophilus, play a critical role in supressing the growth of pathogenic bacteria in the gut. Unlike traditional antibiotics, bacteriocins have a narrower range of activity and are more susceptible to degradation by proteases in the gastrointestinal tract [56]. While this limits their direct antimicrobial efficacy, it reduces the likelihood of disrupting beneficial microbiota. It has been demonstrated that several strains of Lactobacillus acidophilus, including L. acidophilus JCM1132, change the makeup of the gut microbiota in healthy mice, lessen inflammatory reactions, and may even prevent metabolic disorders. This demonstrates how bacteriocin-producing strains of probiotics can support gut health [57]. The short-chain fatty acid (SCFA) valeric acid is another significant metabolite that L. acidophilus produces. By blocking particular cellular pathways, valeric acid has been shown to decrease the development of non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) [58]. This suggests that L. acidophilus may have a broader role in metabolic health, particularly in the context of liver function. Additionally, L. acidophilus contributes to gut health through the production of exopolysaccharides (EPSs), which have beneficial effects on gut barrier function and immune modulation. These EPSs help maintain the integrity of the intestinal lining and promote a healthy microbiota, further enhancing the bacteriums role in maintaining digestive health [59].

Lactobacillus acidophilus also produces a range of antigenic proteins, including enolase, GroEL (HSP60) and transcription factors like EF-Ts and EF-Tu. Serum IgG antibodies in children, especially those with autoimmune diseases like coeliac disease and type 1 diabetes, recognise these proteins. This suggests that L. acidophilus may have a complex interaction with the immune system, potentially influencing autoimmune responses or contributing to the development of these conditions through immune modulation. Additionally, L. acidophilus 5e2 produces exopolysaccharides (EPSs) composed of galactose, glucose and glucosamine [60]. These EPSs may promote gut health by fostering beneficial microbial communities, supporting a balanced microbiota, and enhancing the gut barrier function. The production of bio surfactants such as surlactin by Lactobacillus species also plays a role in protecting the gut. Surlactin reduces surface tension and inhibits pathogen adhesion, thus preventing harmful microorganisms from colonizing the gut and maintaining a healthy microbiome. Together, these metabolic and immune-modulatory effects of L. acidophilus underscore its significant role in maintaining gut health, modulating the immune system, and potentially contributing to the prevention of autoimmune conditions. The bacteriums ability to produce EPSs, bio surfactants, and antigenic proteins highlights its multifunctional role as a probiotic microorganism [61,62].

Saccharomyces boulardii:  Probiotic yeast is well known for its medicinal properties, especially in relation to gastrointestinal health. Recent research has deepened our understanding of the many metabolites that S. boulardii produces, illuminating its possible uses as a microbial cell factory, in the treatment of cancer, and in gastrointestinal problems. A variety of bioactive metabolites, including polyphenolic chemicals like vanillic acid, cinnamic acid, and phenylethyl alcohol, as well as vital nutrients like vitamin B6, are synthesised by Saccharomyces cerevisiae var. boulardii. These substances support its antioxidant activity and serve as the foundation for its antiviral, antibacterial, anticarcinogenic, and overall health-promoting qualities. S. boulardii also generates compounds that improve its therapeutic profile, such as amphetamine and erythromycin. Saccharomyces boulardii, particularly strain S. boulardii-B508, produces a crucial molecule called Saccharomyces anti-inflammatory factor (SAIF) [63]. By causing apoptosis in infected cells and suppressing NF-κB activation, this factor has been demonstrated to lower the load of Mycobacterium intracellular in human macrophages. SAIFs suppression of NF-κB, a crucial regulator of the human inflammatory response, aids in gastrointestinal tract inflammation reduction. In order to lessen the harmful effects of endotoxins like Escherichia colis lipopolysaccharide (LPS), S. boulardii also produces a phosphatase that can dephosphorylate them [64,65]. Additionally, it generates a 54-kDa serine protease that restricts the release of water and electrolytes and reduces intestinal permeability, improving its defence against bacterial toxins and reducing inflammation in the gastrointestinal tract. The capacity of S. boulardii to produce large amounts of acetic acid at 37°C is a distinctive feature that is associated with certain mutations in the SDH1 and WHI2 genes that are absent from S. cerevisiae. These genetic characteristics increase the yeasts effectiveness as a probiotic by allowing it to flourish in acidic surroundings and offering resilience to stomach disorders [66].

Furthermore, Clostridium difficile toxin A is broken down by a serine protease produced by S. boulardii, which also promotes the generation of antibodies against the toxin and reduces inflammation by boosting anti-inflammatory molecules such as peroxisome proliferator-activated receptor-gamma (PPAR-γ) [67,68]. This highlights S. boulardiis potential role in treating C. difficile infections and modulating gut inflammation. Saccharomyces boulardii demonstrates a broad spectrum of beneficial properties through its production of bioactive metabolites, including antioxidants, anti-inflammatory factors, and antimicrobial peptides. Its unique genetic traits and metabolic activities make it an effective probiotic, with significant potential in treating gastrointestinal disorders and supporting overall gut health [69].

Mechanisms of Action and Types of Probiotic Metabolites in Children:

At birth, a newborns intestine is sterile, but during the birthing process and the first few days of life, it becomes colonized with bacteria, primarily Enterobacteria. In breastfed infants, Bifidobacteria rapidly proliferate, constituting 80-90% of the gut flora, whereas formula-fed infants have a more complex flora with fewer Bifidobacteria [70]. Probiotic metabolites, the bioactive compounds produced by beneficial microorganisms, play an essential role in enhancing and maintaining childrens health. These metabolites, which include short-chain fatty acids (SCFAs), bacteriocins, exopolysaccharides (EPSs), and vitamins, among others, provide numerous health benefits to the host. Understanding the different types of probiotic metabolites and their mechanisms of action is crucial for maximizing their therapeutic potential. This section examines various probiotic metabolites and the specific ways they promote health in children. Exopolysaccharides (EPSs) are complex carbohydrate polymers secreted by probiotics that support the growth of beneficial bacteria, improve gut barrier function, and exhibit antioxidant, immune regulatory, and anti-inflammatory properties. EPSs enhance the production of short-chain fatty acids, further contributing to gut health. Vitamins synthesized by probiotics, including various B vitamins and vitamin K, are essential for energy metabolism, DNA synthesis, and overall growth and development in children [71,72]. These vitamins also support the nervous system, promote blood clotting, and strengthen bones [73]. SCFAs, such as acetate, propionate, and butyrate, are produced during the fermentation of dietary fibres by gut bacteria [74]. These metabolites nourish intestinal cells (colonocytes), strengthen the gut barrier, regulate the immune system, and exhibit anti-inflammatory properties, reducing the risk of colic, gastrointestinal infections, and inflammatory bowel disease in children [75,76]. Bacteriocins are antimicrobial peptides produced by probiotic bacteria that can inhibit the growth of pathogenic microorganisms. This helps maintain a healthy gut microbiota balance and reduces the risk of infections (Table 1). By leveraging the full potential of these probiotic metabolites, we can significantly improve the health and well-being of children, supporting their growth, development, and immune function [77,78]. Continued research into these bioactive compounds and their mechanisms of action will help optimize their use in paediatric healthcare [79,80].

 

 

Vitamins: Beneficial microorganisms create bioactive substances called probiotic metabolites, which are essential for fostering and preserving childrens health. These metabolites have a number of beneficial impacts on the host, including vitamins, bacteriocins, short-chain fatty acids (SCFAs), and exopolysaccharides (EPSs) [81]. Leveraging the full therapeutic potential of these probiotic metabolites requires an understanding of their kinds and modes of action. The several kinds of probiotic metabolites are examined in this section, along with the precise methods by which they benefit childrens health. Probiotic bacteria play a crucial role in synthesizing essential vitamins that impact childrens health and development. Certain strains of lactic acid bacteria (LAB) and bifidobacteria produce vitamins necessary for growth, development, and immune function [82,83,84]. Probiotic bacteria synthesize several B vitamins, including B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate), and B12 (cobalamin) (Abdou et al., 2022) [85,86]. These vitamins are necessary for energy metabolism, DNA synthesis, the formation of red blood cells, and the function of the nervous system; strains such as Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus reuteri, Lactobacillus rhamnosus, and Streptococcus thermophilus, GG, are effective at producing B vitamins and can improve the nutritional profile of foods; probiotic bacteria also synthesise vitamin K, especially in its K2 form (menaquinone), which is essential for blood clotting, bone health, and cardiovascular function; known producers of vitamin K2 include Bacillus clausii and Lactococcus lactis; neonatal gut bacteria include Enterobacter agglomerans, Serratia marcescens, and Enterococcus faecium, which also contribute to vitamin K production [87]. Vitamin absorption and bioavailability can be improved by probiotics. According to studies, taking probiotic supplements improves gut health indicators and raises blood levels of vitamins D and A [88]. Probiotics may control gene expression and improve food absorption while supporting a number of physiological functions, such as immune response, energy metabolism, and bone mineralisation [89].

Short-Chain Fatty Acids (SCFAs): Childrens gut health is supported by short-chain fatty acids (SCFAs), which include butyrate, propionate, and acetate. By supporting colonocytes, the cells that line the intestines and help create a robust barrier that keeps dangerous chemicals out of the circulation, they are vital for preserving a healthy digestive tract. Furthermore, butyrate has anti-inflammatory qualities that guard against illnesses including colic, gastrointestinal infections, and inflammatory bowel disease. SCFAs are also essential for the immune systems growth, modulation, and maturation [90,91].

Probiotic strains like Lactobacillus and Bifidobacterium are known to produce SCFAs in the gut; these beneficial bacteria are commonly found in fermented foods like yoghurt or in dietary supplements formulated for children. When children consume probiotic-rich foods, these bacteria proliferate in the gut and produce SCFAs by fermenting dietary fibres found in fruits, vegetables, and whole grains [92]. SCFAs help maintain an optimal gut environment by lowering the pH, which supports the growth of beneficial bacteria while inhibiting harmful pathogens. They also improve the gut barrier by encouraging the production of mucins, which shield the gut lining and prevent pathogen adherence and invasion [93].

Antimicrobial Peptides: The body and some probiotic bacteria create tiny, naturally occurring antibiotic molecules called antimicrobial peptides (AMPs). By altering gut microbiota and offering protection from infections, they present a viable strategy for improving childrens health. AMPs, such as bacteriocins, are safer for treating paediatric infections and fostering gut health because they selectively inhibit dangerous bacteria while fostering good microorganisms and have a lesser chance of acquiring resistance than traditional antibiotics [94,95]. Numerous research indicate that probiotic-derived AMPs may be used as therapeutic agents for children, despite the paucity of direct data supporting their use in paediatric health. Research has highlighted the broader benefits of probiotic-derived AMPs, including immunomodulatory, antimicrobial and microbiota-regulating properties [96]. Clinical trials have shown the effectiveness of cationic antimicrobial peptides in managing paediatric infections, particularly those involving antibiotic-resistant pathogens. Further research on probiotic-derived AMPs could lead to innovative, safe, and effective treatments for infections and improved health outcomes in children [97,98].

Enzymes: Probiotic-produced enzymes are essential for boosting childrens health since they aid in digestion and enhance nutrient absorption. By breaking down complex nutrients, these helpful microbes help a childs developing digestive system absorb them more easily and support a healthy gut environment, which is essential for growth, immune system function, and general health. An essential enzyme that increases the efficiency of probiotics in the stomach is β-glucosidase, which converts complex carbs into simpler sugars [99]. To break down milk-based diets, Bifidobacterium species create β-galactosidase, which cleaves lactose into glucose and galactose. This enzyme also forms beneficial prebiotics called galactooligosaccharides (GOSs) [100, 101]. Lacto-N-biosidase (LNBase), primarily found in Bifidobacterium spp., helps digest human milk oligosaccharides (HMOs) into simpler forms for the infants gut microbiota, improving gut health and potentially alleviating food allergies. Overall, the enzymatic activities of probiotics enhance nutrient absorption, digestion and gut microbiota composition, significantly contributing to infant and child health. Continued research into probiotic-derived enzymes is essential for enhancing paediatric health outcomes [102, 103].

Exopolysaccharides (EPSs): Lactobacillus, Bifidobacterium, Streptococcus, and Weissella are probiotic bacteria that release complex carbohydrate polymers called exopolysaccharides (EPSs). They are homo or hetero polysaccharides made up of repeating units of glucose, galactose, mannose, and rhamnose [104].  EPSs can be covalently anchored to the cell surface or secreted into the extracellular environment, forming a mucilaginous layer that aids in bacterial biofilm development. EPSs have bifidogenic activity, selectively stimulating the growth of Bifidobacterium species, which are dominant in infants gut microbiota [105]. They act as prebiotics, resisting digestion in the upper gastrointestinal tract and serving as substrates for beneficial gut bacteria in the colon. EPSs exhibit various biological activities, including free radical scavenging, antioxidant properties and reduction of oxidative stress [106]. They also have immunoregulatory effects, enhancing macrophage activity and reducing inflammatory markers. Additionally, EPSs from probiotics show antitumor, antibacterial, antiviral, and lipid regulation properties. They improve adherence and colonization of beneficial microflora on host cells. Overall, EPSs are promising candidates for functional foods and therapeutic agents aimed at enhancing childrens health [107, 108].

Neurotransmitters: Childrens brain growth, emotional control, and cognitive processes like memory and learning all depend on gamma-aminobutyric acid (GABA). It lowers anxiety, encourages sound sleep, and manages stress by balancing the brains excitatory and inhibitory impulses. Emotional stability, behavioural control, and brain circuit development are all supported by adequate GABA levels [109]. Lactobacillaceae and Bifidobacterium species are primary producers of GABA, with the latter being the most efficient. GABA is produced by the enzyme glutamate decarboxylase (GAD), converting l-glutamate into GABA and contributing to the guts acid-base balance. GABA-producing probiotics impact the gut-brain axis, influencing gut motility, secretion, and blood flow, and may affect the central nervous system via the vagus nerve, reducing stress and anxiety-like behaviors [110]. Studies show that gut microbiota diversity in children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) undergoes significant changes [111]. Lower GABA levels are linked to these conditions. Clinical trials suggest that probiotics containing GABA-producing Bifidobacterium or Lactobacillaceae species can effectively treat gastrointestinal issues and enhance mental health in children [112, 113].

Other neurotransmitters produced by probiotics can significantly influence host health via the gut-brain axis. For example, certain probiotic strains synthesize serotonin, which regulates mood, appetite, and sleep. Bacillus and Lactobacillus species produce dopamine, affecting neurological functions and behavior. Lactobacillus plantarum produces acetylcholine, important for learning, memory, and muscle activation. Probiotics like Escherichia coli and Bacillus subtilis can synthesize norepinephrine, involved in alertness and stress responses, and Lactobacillus reuteri produces histamine, which is critical for immune responses and gut motility [114]. Lactobacillus and Bifidobacterium strains produce glutamate, an excitatory neurotransmitter important for synaptic plasticity. This ability to synthesize neurotransmitters supports probiotics potential role in managing neuropsychiatric and gastrointestinal disorders by modulating the gut-brain axis [115].

Bioactive Postbiotic Fractions: According to the ISAPP, postbiotics are inanimate bacteria and their constituent parts that have therapeutic value. Postbiotics, in contrast to probiotics, are made up of healthy by products such as lipids, proteins, carbs, vitamins, and organic acids rather than live bacteria. These substances can be added to functional foods like baby formulae and are present in foods like yoghurt, kefir, and pickled vegetables. Compared to probiotics, postbiotics are easier to store, more stable, and have a longer shelf life [116].

 They play  important role in childrens health by supporting gut balance, boosting immunity, reducing inflammation, enhancing nutrient absorption, and protecting against infections. Postbiotics also have fewer safety concerns compared to probiotics, making them suitable for vulnerable populations [117,118]. Postbiotics demonstrate strong immunomodulatory and anti-inflammatory effects via activating immunological receptors such Toll-like receptors (TLRs). They can lessen inflammatory reactions and improve both innate and adaptive immune responses. Postbiotic-containing fermented infant formulae have been the subject of recent studies, which have demonstrated beneficial effects on newborns immune systems and gut microbiota composition [119,120].

Clinical Evidence on Probiotics in Child Health:

Probiotics in Gastrointestinal Disorders:

Necrotizing Enterocolitis (NEC): Necrotizing Enterocolitis (NEC) is a severe intestinal condition primarily affecting preterm, very-low-birth-weight infants, characterized by intestinal inflammation and necrosis. It has high morbidity and mortality rates, leading to increasing interest in its risk factors, pathophysiology, diagnostic methods, and treatment options. NEC results from factors like early gestational age, low birth weight, and artificial feeding, causing gut microbiota dysbiosis and immature immune responses [121]. Early diagnosis is critical to reducing its incidence and mortality. The pathophysiology of NEC is poorly understood, but it may involve premature intestinal over activation to bacterial antigens, leading to mucosal destruction and mesenteric perfusion deterioration. Therapeutic strategies mainly focus on preventing gut dysbiosis through feeding protocols favouring breastmilk, controlled antibiotic use, and probiotics. A recent meta-analysis found that probiotics like Lactobacillus acidophilus LB were effective in reducing NEC risk in both breastfed and formula-fed preterm infants [122]. Other strains like Bifidobacterium lactis Bb-12/B94 also reduced mild/severe NEC risk [123]. However, the evidence remains limited, as studies had small populations, varied probiotic strains, and inconsistent treatment protocols. Probiotic therapy should be used cautiously in preterm infants due to their immature immune and gastrointestinal systems, avoiding strains with transferable antibiotic resistance genes [124]. The mechanisms of probiotics in NEC treatment are not fully understood but may include modulating the NF-κB-dependent inflammatory response, enhancing gut barrier function, reducing pathogen growth, and mitigating oxidative stress and apoptosis. Studies also suggest that probiotics might influence immune pathways, such as the TLR9-mediated signaling and the PXR-JNK pathway, enhancing tight junction and antimicrobial peptide expression, thus protecting the intestinal barrier.

Helicobacter pylori Infection: Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects the stomach and duodenal mucosal layers. It affects over half of the global population, with higher prevalence in developing countries [125]. While infection often occurs asymptomatically in childhood, it later leads to conditions like peptic ulcer disease (PUD) and gastric cancer (GC) [126]. Its incidence has decreased in children due to better healthcare and living standards. Although the pathophysiological mechanisms are not fully understood, research suggests a connection between H. pylori infection and NF-κB-dependent chronic gastric inflammation. H. pylori antigens trigger TLR receptors on epithelial cells, activating NF-κB and JNK pathways, which increases pro inflammatory cytokines and chemokines [127]. The virulence factor CagA also activates the bacterial-type secretion system and NF-κB, exacerbating inflammation and leading to more severe gastritis, PUD, and GC. Diagnosis of H. pylori infection is based on non-invasive methods, including serologic tests, urea breath tests, or stool antigen tests [128]. Treatment typically involves triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor for 14 days, followed by monitoring with non-invasive tests [129].  However, due to increasing antibiotic resistance, new treatments like probiotics are being explored. A systematic review by Losurdo et al. found that probiotics eradicated H. pylori in 14% of patients, with slightly higher success rates for Lactobacilli-based therapies (16%) [130]. Meta-analyses also suggest that probiotics, when combined with traditional treatments, improve eradication rates and reduce side effects (Sung et al., 2020). Probiotics may inhibit H. pylori adherence to gastric cells, modulate the NF-κB pathway, and downregulate pro-inflammatory mediators like IL-8, COX-2, and nitric oxide [131]. Some studies also show that certain Lactobacillus strains can activate anti-inflammatory pathways. Although further research is needed, probiotics are recommended as adjunctive therapy to enhance H. pylori eradication and immune responses [132].

Role of Probiotics in Acute Infectious Diarrhoea and Antibiotic-Associated Diarrhoea in the Child Population: Acute infectious diarrhoea (AID) is a common paediatric condition, often caused by microorganisms like rotavirus, Escherichia coli, Salmonella spp., and others. It typically lasts a few days but can lead to severe dehydration, weight loss, and potential life-threatening complications [133]. Pathogens involved in AID often disrupt fluid and electrolyte absorption in the intestine. Some pathogens like rotavirus and V. cholerae secrete enterotoxins that impair electrolyte transport, causing watery diarrhoea, while others like Shigella spp. and Campylobacter jejuni cause inflammatory diarrhoea with bloody stools and abdominal pain [134]. There is no specific treatment for AID, but oral rehydration therapy with reduced or hypotonic osmolarity solutions is recommended, along with dietary modifications and continued breastfeeding (WHO, 2019). Probiotics have been suggested as an adjunct to rehydration therapy. The 2023 ESPGHAN guidelines recommend specific probiotic strains for AID treatment, including Lacticaseibacillus rhamnosus GG, Saccharomyces boulardii, and Limosilactibacillus reuteri DSM 17938, but caution against the use of certain other strains like Lactobacillus helveticus R0052 (Murray et al., 2023). Probiotics like L. rhamnosus GG have shown to reduce diarrhoea duration, stool frequency, and hospital stays, particularly when given early in infection. Saccharomyces boulardii is also effective in reducing diarrhoea duration and vomiting [135].  However, the evidence for L. reuteri DSM 17938 is inconclusive, with the need for further high-quality studies to clarify its effectiveness [136]. Probiotics are believed to work through direct and indirect mechanisms, including enhancing intestinal mucosal integrity, modulating immune responses, producing antimicrobial compounds like bacteriocins and short-chain fatty acids (SCFAs), and improving gut barrier function [137]. However, there is a lack of consensus on their effectiveness, with some organizations like the American Gastroenterological Association and Cochrane not supporting their use for AID treatment [138].  Antibiotic therapy is not routinely recommended for AID, except for specific pathogens like Shigella, enterotoxigenic E. coli, and Vibrio cholerae, as inappropriate use can disrupt gut microbiota and promote pathogen overgrowth. Antibiotic-associated diarrhea (ADD), often due to Clostridioides difficile, is a common complication, especially in patients with chronic conditions. Probiotics, particularly L. rhamnosus GG and S. boulardii, are recommended for ADD prevention, with S. boulardii being effective against C. difficile-related diarrhoea [139]. While the evidence supports probiotics for ADD prevention, more large-scale trials are needed to determine optimal dosages and safety. Other probiotic strains, like Bacillus clausii, are not supported by sufficient evidence for therapeutic use in ADD.

Inflammatory Bowel Disease (IBD): Crohns disease (CD), ulcerative colitis (UC), and unclassified IBD (U-IBD) are all immune-mediated conditions that fall under the umbrella of inflammatory bowel disease (IBD). Genetically predisposed people have an increased immune response to gut microbiota, which is regulated by environmental, immunological, and genetic variables [140]. A diet heavy in fat, sugar, and fibre is also thought to have a role in the development of IBD. The prevalence of IBD in children is rising, and its symptoms include anaemia, poor development, bloody diarrhoea, stomach discomfort, weight loss, and extra-intestinal signs [141]. The primary goals in treating IBD are to eliminate symptoms, improve quality of life, support growth and development, prevent complications, and minimize medication side effects [142].  Paediatric IBD treatment is increasingly personalized based on clinical outcomes, disease severity, patient phenotype, and the impact on growth and psychological health. Treatment often involves a stepped approach using amino salicylates, antibiotics, enteral therapy, and biological immuno-modulators, with surgery being necessary in some acute cases [143]. Nutritional interventions, including monitoring vitamin D, using iron supplements for anaemia, and folic acid supplementation, are crucial for paediatric IBD management [144]. IBD-related microbial dysbiosis and altered dietary habits lead to changes in microbial metabolites and host metabolism. While probiotics have been effective in animal models of colitis, their clinical effectiveness in IBD treatment has been less satisfactory, with limited benefits in certain patients [145]. This may be due to inadequate probiotic strain selection and the impact of excessive inflammation in IBD. VSL#3, a probiotic preparation, has shown some efficacy in children with mild-to-moderate UC. However, more research is needed to identify probiotic strains that can effectively colonize the human gut and overcome the challenges posed by IBD-related inflammation [146]. In addition to probiotics, prebiotics may help by creating nutritional niches in the gut and regulating intestinal immunity. However, few studies on prebiotics in IBD patients have been conducted, and they have not shown significant clinical improvements or adverse effects. Future efforts should focus on personalized probiotic and prebiotic strategies tailored to the individuals microbiome composition and dietary needs for optimal therapeutic results in paediatric IBD patients [147].

Role of Probiotics in Food Allergies: The importance of gut microbiota in the emergence of food allergies (FA) and the promise of targeted bacterial therapeutics for both prevention and therapy have been demonstrated by recent studies. For example, the development of milk protein tolerance at the age of eight is associated with the gut microbiota composition of children between the ages of three and six months [148]. High concentrations of Clostridium and Firmicutes in the gut microbiota of infants who overcome cows milk allergy may be helpful as prospective probiotic strains for milk allergy treatment [149]. While several novel therapeutic strategies have been developed for FA, including allergen- and non-allergen-specific approaches, probiotics have gained significant interest due to their ability to modulate intestinal barrier development and maturation [150]. Probiotics have immunomodulatory effects, such as enhancing Th1 production, suppressing Th2 responses, promoting dendritic cell tolerance, and suppressing IgE production. Furthermore, probiotics may also exert epigenetic modulation of Th1/Th2 gene expression. Another promising concept in FA treatment is postbiotics, which are bioactive soluble products or metabolites from probiotic cultures that maintain biological activity in the host without the risks associated with live probiotic strains. Postbiotics, particularly short-chain fatty acids (SCFAs) like acetate, butyrate, and propionate, have been shown in both in vitro and in vivo studies to enhance epithelial barrier integrity [151]. Mechanisms for this benefit include upregulating tight-junction genes, activating specific protein pathways, generating antimicrobial peptides, and increasing trans epithelial electrical resistance. Additionally, both pro- and postbiotics help maintain gut epithelial integrity by activating innate lymphoid cells (ILC3) and promoting the secretion of mucus and antimicrobial peptides. This reduces the accessibility of food antigens to the systemic circulation, which may lower food allergen sensitization [152]. Despite these advancements, the routine use of probiotics for preventing food allergies is not yet recommended. The European Academy of Allergy and Clinical Immunology (EAACI) guidelines do not endorse or oppose probiotic therapy for FA, as the clinical effects and safety of different probiotic strains are inconsistent. The variability in findings is due to differences in study designs, including population size, treatment duration, probiotic type, and diagnostic criteria. More well-powered, standardized studies are needed to evaluate the effectiveness and safety of probiotics in FA treatment.

Probiotics and Immune System Modulation:

The Role of Probiotics in Immune Responses in Children: Effects on Allergies, Asthma, and Infections

Recent studies have explored the growing potential of probiotics in modulating immune responses in children, particularly with regard to managing immune-related conditions such as allergies, asthma, and infections. Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefits to the host. They have been shown to exert significant effects on the immune system, helping to enhance immune tolerance and balance the immune response, especially in the context of autoimmune diseases, allergic conditions, and infections.

Probiotics and Immune Responses in Children

In children, the developing immune system is highly susceptible to environmental influences, including microbial exposure. Probiotics can influence immune responses by enhancing the function of regulatory T cells (Tregs), which are crucial for maintaining immune tolerance and preventing excessive inflammation. Research indicates that probiotics help increase the number of Tregs, promoting immune tolerance and potentially reducing the risk of autoimmune diseases and allergies [153,154]. For example, a study in children with type 1 diabetes (T1D) found that probiotic supplementation led to an increase in T-regulatory cells and interleukin-10 (IL-10), an anti-inflammatory cytokine that helps regulate immune responses [155]. This immune modulation is significant as it helps to reduce chronic inflammation, a key contributor to many immune disorders. Probiotics may also enhance the gut-associated lymphoid tissue (GALT), where a large portion of immune responses originate, thus strengthening the bodys overall immune defenses [156].

Probiotics in Allergies and Asthma

The treatment of allergic illnesses is one of the most researched applications of probiotics. With diseases like eczema, asthma, and food allergies on the rise, children are especially susceptible to acquiring allergies. The development of the immune system depends heavily on the gut microbiota, and changes in this microbial community have been connected to a higher incidence of childhood allergies [157]. Probiotics have demonstrated potential in immune system modulation to lessen the severity of allergic disorders. Probiotics may specifically affect the Th1/Th2 immunological balance, which is important for allergic reactions. Th2 responses are frequently linked to allergic reactions, whereas Th1 responses offer protection against infections. Probiotics have been shown to reduce allergy sensitisation and the intensity of symptoms by promoting Th1 immunity and inhibiting Th2-driven allergic inflammation [158,159]. To promote overall health and prevent respiratory tract infections (RTIs), it is important to use evidence-based probiotics, such as Lacticaseibacillus rhamnosus GG (formerly known as Lactobacillus rhamnosus), which have been shown to be effective in reducing RTIs. Supporting immune function through a diet rich in fiber and fermented foods like kefir, sauerkraut, and fermented dairy products can help maintain a healthy gut microbiota and boost immunity. Additionally, teaching children good hygiene habits—such as frequent handwashing, proper sneezing and coughing practices, and cleaning shared toys and surfaces—can help reduce the spread of infections, especially in group care settings. Its also crucial to use antibiotics responsibly, limiting their use to situations where they are absolutely necessary, as overuse can disturb the gut microbiota and impair the immune system [160]. For instance, a study of infants with a history of cows milk allergy demonstrated that a specific probiotic strain could help restore a healthy gut microbiota, promoting tolerance to milk proteins and reducing the risk of developing food allergies. Probiotics have also shown promise in reducing asthma exacerbations in children by enhancing the immune response against environmental allergens and improving airway inflammation.

Probiotics in Infections:

In addition to their immune-modulatory effects, probiotics are also beneficial in reducing the risk of infections in children. The gut microbiota plays an important role in defending against pathogens by competing with harmful microbes for nutrients and space. Probiotics help maintain a balanced microbiota, which in turn supports the integrity of the intestinal barrier and prevents the colonization of harmful pathogens. Probiotics have been shown in several trials to help lower the frequency and length of infections, including gastrointestinal, respiratory, and even urinary tract infections in children. For instance, by strengthening the immune system and encouraging the guts synthesis of antimicrobial peptides, probiotics have been shown to lower the frequency of acute respiratory infections [161]. Probiotics also aid in the respiratory tracts optimum immune response development, which strengthens childrens defences against illnesses. Moreover, probiotics have shown efficacy in managing gastrointestinal infections, particularly those caused by rotavirus and other pathogens. They help restore the balance of gut microbiota during and after an infection, reducing inflammation and promoting faster recovery. In paediatric populations, this can be particularly important in managing infections and preventing long-term gastrointestinal disturbances [162]. Probiotics offer significant potential in modulating immune responses in children, particularly in the context of allergies, asthma, and infections. Through their immunomodulatory effects, probiotics can help enhance immune tolerance, restore a balanced Th1/Th2 response, and support the development of the gut-associated immune system. By improving immune function, probiotics not only help reduce the risk and severity of allergic diseases such as asthma and food allergies but also provide protection against a range of infections. However, further research and well-designed clinical trials are needed to fully understand the mechanisms through which probiotics influence immune responses and to establish standardized guidelines for their use in paediatric populations.

Probiotics in Neonates and Infants:

Promoting Healthy Gut Flora and Preventing Early Childhood Disorders

The first years of life are crucial for establishing a healthy gut microbiota, which plays an essential role in the development of the immune system and overall health. Probiotics—live microorganisms that confer health benefits when administered in adequate amounts—have gained significant attention for their potential to influence gut flora in neonates and infants, promoting long-term health outcomes. In this paper, we will explore the use of probiotics in early childhood, specifically their role in promoting healthy gut flora and their potential benefits in preventing infantile colic, allergies, and other early childhood disorders [163].

The Role of Probiotics in Promoting Healthy Gut Flora in Neonates and Infants

The human gastrointestinal (GI) tract is initially sterile at birth, and the colonization of microbes begins during and immediately after delivery. In neonates, the gut microbiota is influenced by several factors, including mode of delivery (cesarean section or vaginal birth), diet (breastfeeding or formula feeding), and environmental exposures. Early colonization of beneficial microbes is critical for the development of a balanced gut microbiota, which can enhance immune function, support digestion, and prevent the colonization of pathogenic organisms [164]. Probiotics, specifically certain strains of Lactobacillus, Bifidobacterium, and Streptococcus, have been shown to help establish a healthy gut flora in infants. Research indicates that administering probiotics during the early stages of life can accelerate the establishment of beneficial bacteria, particularly Bifidobacterium species, which are considered important for gut health and immune development [165]. The early colonization of these microbes is associated with improved gut barrier function, regulation of inflammation, and enhanced immune tolerance, all of which play a role in promoting long-term health.

Breastfeeding, which naturally supports the development of a healthy gut microbiota, has been shown to promote the growth of beneficial microbes such as Bifidobacteria. However, in infants who are not breastfed or in those who have conditions that hinder proper microbial colonization, probiotic supplementation can help promote the growth of these beneficial microbes and support the development of a healthy gut microbiota [166].

Probiotics and the Prevention of Infantile Colic

Infantile colic, characterized by excessive crying and irritability in infants, is a common issue faced by parents during the first few months of life. Although the exact cause of colic is unknown, it has been suggested that gut dysbiosis (an imbalance of gut microbiota) and gastrointestinal discomfort could play a role in its development. Some studies have suggested that probiotics, particularly Lactobacillus reuteri, may help alleviate symptoms of infantile colic by improving gut function and reducing inflammation.

A well-known study by Savino [167] found that Lactobacillus reuteri supplementation significantly reduced crying time in infants with colic. The researchers hypothesized that the probiotic strain helped improve gut motility, reduce gas production, and enhance the overall gut microbial balance, which alleviated symptoms of colic. These findings suggest that probiotics may offer a safe and effective treatment option for managing colic in infants.

Probiotics and the Prevention of Allergies in Early Childhood

The development of allergies, such as food allergies, eczema, and asthma, is influenced by the balance of the immune system and the gut microbiota. A growing body of evidence suggests that early microbial exposure plays a critical role in modulating immune responses, and that an imbalance of gut microbiota (dysbiosis) during early life may contribute to an increased risk of developing allergies.Probiotics, by promoting the growth of beneficial bacteria in the gut, may help to reduce the risk of allergies in infants. Research indicates that probiotics can help enhance the development of immune tolerance, particularly by promoting the function of regulatory T cells (Tregs), which are essential for preventing excessive immune responses that lead to allergies [168]. Furthermore, probiotics may help modulate the Th1/Th2 immune balance, which plays a crucial role in the development of allergic diseases. By promoting Th1 responses and suppressing Th2-driven inflammation, probiotics may reduce the risk of allergic sensitization in infants.

Several clinical trials have examined the effects of probiotics on the prevention of allergic conditions in infants. A study by Kalliomäki [169] demonstrated that probiotics administered to pregnant women and their infants reduced the incidence of eczema in the first two years of life. Similarly, other studies have shown that probiotics may reduce the risk of food allergies, particularly in infants with a family history of allergic diseases [170].

Other Potential Benefits of Probiotics in Neonates and Infants

In addition to promoting healthy gut flora and preventing conditions like colic and allergies, probiotics have been studied for their role in preventing other common health issues in neonates and infants. For instance, probiotics have been found to be effective in preventing and treating gastrointestinal infections, such as diarrhoea caused by rotavirus and other pathogens [171]. In hospitalized neonates, probiotics may help reduce the risk of necrotizing enterocolitis (NEC), a severe gastrointestinal condition that primarily affects premature infants [172]. Probiotics are also believed to support the development of a healthy gut microbiota in preterm infants, who are at greater risk of developing gut-related complications.

Probiotics have shown significant promise in promoting healthy gut flora and preventing a range of health conditions in neonates and infants. Early supplementation with probiotics can help establish a balanced gut microbiota, which is crucial for the development of the immune system and overall health. Probiotics have been shown to be beneficial in preventing infantile colic, reducing the risk of allergies, and supporting gastrointestinal health in infants. Although further research is needed to better understand the optimal probiotic strains, dosages, and timing of administration, probiotics offer a safe and effective approach to supporting early childhood health.

Probiotics in Childrens Health: Mechanisms, Benefits, and Sources

Probiotics play a critical role in supporting gut health, immune function, and overall well-being in children. At birth, a babys gut is sterile, but it rapidly acquires beneficial bacteria from the environment, primarily through breastfeeding and later, the introduction of solid foods. These beneficial bacteria aid in food digestion, nutrient absorption, and the development of the immune system [173]. Probiotic supplements can be especially valuable in situations where the natural colonization of the gut is compromised, such as in premature infants or those who have been administered antibiotics. Specific strains of probiotics can help restore a healthy gut microbiome, supporting overall health [174]. For older children, probiotics continue to support the body by maintaining a balanced gut microbiota, which is essential for several health functions, including immune support and digestive assistance. Probiotics support the immune system by promoting the growth of beneficial bacteria and reducing inflammation [175]. They help balance the gut ecosystem by increasing the number of beneficial bacteria, which in turn crowd out harmful pathogens and prevent infection [176]. Additionally, probiotics assist with digestion by promoting intestinal integrity and nutrient transport mechanisms [177].

Types of Probiotics for Children

Probiotics and prebiotics are offered as supplements in liquid, powder, tablet, and capsule form (Fig.1). However, bear in mind that the US Food and Drug Administration does not regulate supplements. This indicates that there are no formal rules on the amount to be taken or for how much time. Before giving your kid any supplements, such as probiotics or prebiotics, be sure to see your paediatrician. Probiotics for children are available in various forms, each offering unique advantages:

1. Probiotic Drinks: These often come in yogurt-based beverages that are easy to incorporate into a childs daily routine. Probiotic drinks are typically rich in essential nutrients like calcium and vitamin D, which are important for a growing childs development. Furthermore, they contain live cultures that provide health benefits [178]. They are available in various flavours, making them more appealing to children.
2. Probiotic Powders: These powders are versatile and can be mixed into foods such as smoothies, cereal, or yogurt without significantly altering taste. Powders also offer the advantage of easy dosage control, allowing parents to adjust the amount according to the childs needs. Additionally, probiotic powders typically have a longer shelf life and do not require refrigeration, making them convenient for busy families and travel [179]
3. Probiotic Gummies: Probiotic gummies are a fun, tasty, and convenient way for children to receive their daily dose of probiotics. They are available in multiple flavours, which helps increase compliance in children who may be resistant to other forms of supplementation. However, parents should choose low-sugar or sugar-free options to avoid excessive sugar intake [180].

 

 

Natural Food Sources of Probiotics

In addition to supplements, several natural food products are rich in probiotics:

• Yogurt: A well-known source of probiotics, particularly when labeled as containing live and active cultures. Yogurt can be consumed plain or with toppings such as fruit or granola, making it a versatile food for children [181].
• Kefir: A fermented dairy product similar to yogurt but with a thinner consistency. It contains a diverse range of probiotic strains and is generally well-tolerated by children [182].
• Fermented Vegetables (e.g., Pickles, Kimchi): These fermented foods are another excellent source of probiotics. However, it is important to check the ingredient list to ensure the presence of live cultures, and be mindful of potential allergens [183].

Probiotics play a pivotal role in the health of children by supporting gut health, immune function, and digestion. Whether through probiotic supplements or naturally fermented foods, incorporating these beneficial microorganisms into a childs diet can offer numerous health benefits. With various forms of probiotics available—such as drinks, powders, and gummies—parents can choose the best option for their childs preferences and lifestyle. However, it is crucial to ensure that the products contain live cultures and to choose those with minimal added sugars.

Safety Evaluation of Probiotics for Children of Different Age Groups

Probiotics are generally considered safe for children, but their use should be tailored to age groups and health conditions. The safety profile can vary depending on the childs age, underlying health conditions, and the specific probiotic strain used. For infants and toddlers, probiotics have been shown to be beneficial in supporting gut health, especially in cases where the gut microbiota may be compromised, such as in premature infants or those who have received antibiotics [184]. In older children, probiotics mainly help maintain a balanced gut microbiota, supporting immune function and aiding digestion. However, as childrens immune systems develop at different rates, special care should be taken when administering probiotics to children with compromised immunity.

In Immunocompromised Children: Probiotics should be used with caution in children with weakened immune systems, such as those undergoing chemotherapy, taking immunosuppressive medications, or living with conditions like HIV or cystic fibrosis. In such cases, there is a theoretical risk that the probiotic bacteria could cause infections, particularly with certain strains of Saccharomyces boulardii (yeast-based probiotics), which have been associated with rare cases of fungemia [185]. Always consult with a healthcare provider before starting probiotics in children with compromised immune systems.

Risk Associated with Improper Use of Probiotics

Probiotics, when misused or improperly dosed, may lead to some unwanted side effects, although serious adverse events are rare. For most children, probiotics are well-tolerated, but some may experience mild gastrointestinal symptoms such as increased gas, bloating, or changes in bowel movements, especially when starting supplementation [186]. These effects are usually short-lived and subside as the childs digestive system adjusts. However, if symptoms persist or worsen, it is advisable to discontinue use and consult with a paediatrician.

Probiotics containing Saccharomyces boulardii (yeast-based probiotics) can sometimes cause additional side effects such as increased thirst or constipation. These symptoms can typically be addressed by adjusting the dosage, but any discomfort should be monitored closely [187]. In rare instances, some children may develop skin rashes or itching of the eyes, potentially indicating an allergic reaction to certain strains of probiotics. If these symptoms occur, the probiotic should be discontinued, and a paediatrician should be consulted to determine whether a different strain may be more appropriate.

Recommended Dosage and Precautions When Giving Probiotics to Children

The appropriate dosage of probiotics for children can vary depending on age, health status, and the specific strain of probiotics being used. The recommended dose generally ranges from 1 to 10 billion CFUs (colony-forming units) per day for children, although lower doses may be appropriate for younger children or those with specific health concerns [188]. It is crucial to follow the dosage instructions provided on the product label or as prescribed by a healthcare professional.

When introducing a probiotic supplement, it is recommended to start with a lower dose and gradually increase it to allow the childs digestive system to adjust. This gradual increase helps minimize the risk of gastrointestinal side effects like bloating or gas. Additionally, parents should ensure they choose probiotic products that are specifically formulated for children, as these products generally contain strains that are safe and beneficial for young children.

Precautions:

1. Consult a Paediatrician: Always consult with a healthcare provider before starting a probiotic, especially for children with underlying health conditions or compromised immune systems.
2. Monitor for Side Effects: Observe the child for any signs of adverse reactions, such as allergic responses (e.g., skin rashes or itching) or gastrointestinal discomfort (e.g., excessive bloating or diarrhoea).
3. Choose the Right Strain: Not all probiotics are the same. Choose products with strains that have been specifically studied and shown to be safe and effective for children, such as Lactobacillus rhamnosus GG or Bifidobacterium bifidum [189].
4. Avoid Excessive Use: Avoid giving high doses of probiotics or using them for extended periods without guidance from a healthcare provider. Long-term, unnecessary use may disrupt the natural balance of gut bacteria and have unintended effects on health.

Probiotics can provide numerous benefits to children, supporting digestive health and immunity, but their use should be carefully monitored. While the side effects are generally mild, improper use, especially in children with compromised immune systems or those receiving yeast-based probiotics, can pose risks. Adhering to recommended dosages, starting with low doses, and consulting a healthcare provider for children with specific health concerns or conditions is essential to ensure safety and effectiveness.

Conclusion

In conclusion, probiotics offer a promising approach to support childrens digestion, immunity, and facilitate overall health. The growing body of evidence suggests that certain probiotic strains can effectively address common paediatric health issues such as diarrhoea, constipation, and colic, while also promoting a healthy gut microbiome. The various forms of probiotic supplementation, including powders, gummies, liquids, and drops, provide flexibility in administration, making it easier to integrate probiotics into childrens daily routines. However, it is essential to recognize that not all probiotics are equally effective, and selecting the right strain, dosage, and form for a childs specific health needs is crucial. While probiotics are generally considered safe for children, there remain areas of concern, including the need for further research on long-term effects, optimal dosages, and the potential risks of overuse. Parents and caregivers should consult with healthcare professionals before introducing probiotics into a childs regimen, particularly for infants or children with underlying health conditions. Ultimately, probiotics represent a valuable tool in paediatric health, but careful consideration and individualized care are necessary to maximize their benefits. Continued research will further clarify the full range of benefits and guide evidence-based recommendations for their use in children.

Acknowledgements: The authorsare grateful to Professor Jayanand, PVC for helping in the preparation of the manuscript.

Funding Sources: No financial assistance was obtained

Conflict of Interest: The authorsdeclare no conflict of interest