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Role and need of pre-biotics and probiotics in the evolving gut microbiome
*Corresponding author: Bakul Jayant Parekh, Department of Pediatrics, Bakul Parekh’s Children’s Hospital, Mumbai, Maharashtra, India. drbakulparekh55@gmail.com
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How to cite this article: Parekh BJ, Kesavelu D. Role and need of pre-biotics and probiotics in the evolving gut microbiome. Karnataka Paediatr J. 2025;40:102-8. doi: 10.25259/KPJ_22_2025
Abstract
The gut microbiota is pivotal in the development of various systems in the human body, and it has been understood that it plays a significant role in the formation and functioning of all these systems, including the gut–brain axis. The human gut microbiota is influenced by multiple factors, including amniotic fluid, mode of delivery, type of feeding, and the use of antibiotics in the first few months of life, with the list becoming endless as numerous factors contribute to its significance. This article aims to look at the pre- and post-biotics in the development of the human gut microbiome.
Keywords
Dysbiosis
Infant
Microbiome
Pre-biotics
Probiotics
INTRODUCTION
The gut microbiome is currently being extensively researched and recognised as playing a critical role in the management and prevention of diseases. Several bidirectional communication pathways, such as the gut-brain, gut-bone, gut-immunity, gut-lung and gut-skin axis, establish the gut as a central organ for metabolic, immunological and cognitive development and regulatory functions.
The foundation of a healthy gut microbiome is established in early infancy, making this period crucial for targeted interventions. The early colonisers of the microbiome are influenced by factors such as mode of delivery, choice of infant feeding, maternal antibiotic exposure, diet and multiple host-environmental interactions. Microbial balance determines overall health, while dysbiosis (microbial imbalance) is associated with conditions such as functional gastrointestinal disorders (FGIDs), allergies, asthma, metabolic syndrome, irritable bowel syndrome, inflammatory bowel disease, and possible neurodevelopmental disorders. Thus, good gut health is essential for overall well-being.[1]
Pre-biotics and probiotics are effective in modulating the gut microbiome to support its optimal development and function. Pre-biotics act as a substrate for beneficial bacteria through fermentation, while probiotics restore microbial balance and enhance immunity. Together, they provide targeted strategies to improve gut health and prevent diseases in humans [Table 1].[2]
| Microbiome / functional feature | Breast-fed infants | Formula-fed infants | Clinical/physiologic implications |
|---|---|---|---|
| Dominant taxa | Bifidobacterium longum subsp. infantis, Bifidobacterium breve, Lactobacillus spp.[12] | Enterobacteriaceae, Clostridium sensu stricto, Streptococcus, Veillonella[12] | Bifidobacteria generate acetate/lactate that lowers luminal pH and inhibits pathogens, whereas facultative anaerobes raise pH and increase endotoxin load |
| α-diversity (within-sample) | Lower during the first 3–6 months, reflecting selective utilisation of HMOs[12,13] | Higher, approaching adult-like heterogeneity[13] | Early low diversity dominated by infant-type bifidobacteria is associated with reduced infection and allergy risk; premature diversification correlates with dysbiosis |
| Faecal pH and SCFA pattern | Mean pH≈5.0–5.5; high acetate±lactate[14,15] | Mean pH≈6.5–7.0; lower total SCFAs; relatively more branched-chain fatty acids[14] | Acidic milieu hinders pathogens and improves mineral absorption; alkaline milieu favours opportunists and proteolytic fermentation |
| Immune markers | Higher secretory IgA coating of microbes and T-reg priming[16,17] | Lower SIgA, skewed Th2/Th17 responses[16] | Better mucosal defence and oral tolerance in breast-fed infants; formula pattern linked to eczema and wheeze |
| Early clinical outcomes | NEC, acute infections, over-weight/metabolic-syndrome risk, allergy[18-20] | NEC, respiratory and GI infections, over-weight risk by 1 y, atopy[18,20] | Differences are largely explained by microbiome-mediated immune and metabolic programming |
| Opportunities for microbiome modulation | HMOs naturally act as selective pre-biotics | Add GOS/FOS or 2'-FL, Bifidobacterium infantis or multistrain synbiotics[21,22] | Targeted supplements can lower faecal pH, enrich bifidobacteria and cut NEC odds by ≥40% |
NEC: Necrotising enterocolitis, SCFAs: Short-chain fatty acids, HMOs: Human milk oligosaccharides, FOS: Fructo-oligosaccharides, GOS: Galacto-oligosaccharides, GI: Gastrointestinal, SIgA: Secretory immunoglobulin A, IgA: Immunoglobulin A, T-reg: Regulatory T cells, FL: Fucosyllactose
FOUR PHASES OF GUT MICROBIOME DEVELOPMENT
The gut microbiome develops in a predictable sequence with distinct milestones:
Phase I – Birth
Colonisation begins at delivery. Vaginal births expose infants to beneficial bacteria, such as Lactobacillus and Bifidobacterium, which are essential for maintaining microbial diversity and supporting immune development. In contrast, caesarean delivery leads to reduced diversity and delayed colonisation of beneficial strains, increasing the risk of FGIDs and immune-related conditions such as allergies and asthma.[3]
Phase II – First 6 months
Feeding plays a crucial role in shaping the early microbiome, impacting immune and metabolic development. Breastmilk provides human milk oligosaccharides (HMOs), which selectively support Bifidobacterium infantis, a bacterium that produces short-chain fatty acids (SCFAs), lowers gut pH, and limits the growth of harmful bacteria. Formula-fed infants develop a more diverse microbiota with greater species variation, including facultative anaerobes. Breastfed infants typically have lower alpha diversity (fewer distinct species initially) but are enriched in beneficial strains, while formula-fed infants exhibit higher alpha diversity and greater inter-individual variation (beta diversity). In the absence of breast milk, it becomes increasingly important to choose the right formula, which includes probiotics, prebiotics, or synbiotics that can support eubiosis.[4]
Phase III – Introduction of complementary feeds
The introduction of solids exposes the gut to novel antigens, diversifying the microbiome. Increased environmental interactions (crawling, teething and mouthing) further modulate gut development, influencing the risk of FGIDs. Fibre-rich fruits and vegetables support SCFA-producing bacteria such as Bacteroides and Prevotella.[5]
Phase IV – Transition to family foods (12-36 months)
By age 2–3, with a full transition to a family diet, the microbiome further develops and stabilises into an adult-like composition [Figure 1].[6]
- Phases of gut microbiome development.
ROLE OF PRE-BIOTICS
Pre-biotics are non-digestible carbohydrates that selectively promote the growth of beneficial bacteria, particularly Bifidobacterium and Lactobacillus. Common prebiotics, such as fructo-oligosaccharides (FOS) and galactooligosaccharides (GOS), have been extensively studied for their role in modulating the gut microbiome. HMOs also function as bioactive pre-biotics.[7] Pre-biotics selectively promote the colonisation of beneficial bacteria. For example, GOS is seen to increase the colonisation of the probiotic Limosilactobacillus reuteri/Lactobacillus reuteri [Figure 2, Table 2].
- Growth of Lactobacillus reuteri DSM 17938 on mMRS (A) supplemented with 2% GOS (●); 2% rhamnose (▲); 2% mixture of GOS and rhamnose (♦); 2% maltodextrin (×); and unsupplemented (●). Results are expressed as means ± SD obtained from three independent replicates.
| Key study | Design and intervention | Microbiome effect | Clinical signal |
|---|---|---|---|
| Wong et al. 2024[23] | RCT, 200 term infants; 9 g/L scGOS: lcFOS (9:1) versus control formula×12 week | Bifidobacterium spp. (×3.4), faecal pH (−0.9) | 30% fewer parent-reported GI infections |
| Wiciński et al. 2020[24] | RCT, 172 formula-fed infants; +1 g/L 2'-FL on GOS/FOS base | Additional 21% rise in bifidobacterial abundance versus GOS/FOS alone | Softer stools; no adverse growth effects |
| De Bruyn et al. 2024[25] | Ex vivo faecal fermentation with 5-HMO blend±Bifidobacterium infantis | Synergistic acetate+propionate (×2) | Mechanistic support for HMO-guided synbiotics |
RCT: Randomised-controlled trials, FOS: Fructo-oligosaccharides, GOS: Galacto-oligosaccharides, HMOs: Human milk oligosaccharides, GI: Gastrointestinal
Figure 2 demonstrates the ability of L. reuteri DSM 17938 to utilise the carbohydrates used in the human trial as growth substrates were tested in vitro. The results demonstrated that GOS supported the growth of the strain, highlighting its role in promoting the colonisation of L. reuteri. However, the strain was unable to ferment rhamnose (an indirect substrate) or maltodextrin (a placebo). Furthermore, when GOS was combined with rhamnose, it did not provide any additional growth advantage to the strain compared to GOS alone. These findings emphasise that GOS is a key factor in increasing the colonisation of L. reuteri.[8]
SCFA PRODUCTION AND BENEFITS
Mechanism
Gut bacteria ferment pre-biotics to produce SCFAs such as butyrate, acetate and propionate.[9]
Benefits
Gut health: SCFAs maintain intestinal barrier integrity by upregulating tight junction proteins, preventing leaky gut syndrome
Immune modulation: SCFAs induce the differentiation of regulatory T-cells, promoting immune tolerance and reducing inflammation
Metabolic regulation: Butyrate provides energy to colonocytes, while propionate influences lipid metabolism and appetite regulation [Figure 3].
- SCFA production and benefits. SCFA: Short-chain fatty acids.
Infographics: Figure 3: SCFA production and benefits.
ROLE OF PROBIOTICS
‘Probiotics are live microorganisms that confer health benefits when consumed in adequate amounts’. They support microbiome balance by promoting beneficial bacteria, inhibiting pathogen adherence, enhancing mucosal immunity and restoring gut homeostasis after dysbiosis [Table 3].[10]
| Key study | Design | Microbiome/immune outcome | Clinical outcome |
|---|---|---|---|
| Fatheree et al. 2017[26] | DB-RCT, 127 breast-fed colicky infants; L. reuteri DSM-17938 (108CFU/d)×28d | Lactobacillus spp., butyrate producers | Median crying time 50% versus placebo |
| Xiaohua L et al. 2025[27] | Network Meta analysis with 2947 children with food allergy | – | L. rhamnosus GG gave the greatest SCORAD reduction (−15 pts) |
| Dai et al. 2025[18] | Meta-analysis, 31 RCTs in pre-terms | Faecal bifidobacteria; dysbiosis index | NEC risk RR 0.54; mortality RR 0.78 |
| PEPS protocol[28] | Ongoing Scandinavian RCT (>1,500 ELBW neonates) | Will link strain-level shifts to NEC/LOS | High-quality data expected 2027 |
PEPS: Probiotics in extreme prematurity in Scandinavia, ELBW: Extremely low birth weight, RR: Relative risk, LOS: Late onset sepsis, NEC: Necrotising enterocolitis, DB-RCT: Double-blind randomised controlled trial, DSM: Deutsche sammlung von mikroorganismen und zellkulturen,GG: Sherwood gorbach and barry goldin, SCORAD:Severity scoring of atopic dermatitis, ELBW: Extremely low birth weight L. reuteri:Limosilactobacillus reuteri/Lactobacillus reuteri, L. rhamnosus: Lactobacillus rhamnosus
APPLICATIONS OF SYNBIOTICS IN EARLY LIFE
The gut–brain axis illustrates the bidirectional communication between the gastrointestinal tract and the central nervous system, mediated by neural, hormonal and immunological pathways. The vagus nerve serves as a primary conduit, transmitting signals between the gut and brain. Gut microbes produce metabolites such as SCFAs and neurotransmitters, which influence brain function by affecting neurotransmitter production, inflammation and synaptic plasticity. Consequently, the gut microbiome profoundly impacts mood, behaviour and cognitive function, with dysbiosis linked to mental health disorders and neurodegenerative diseases [Table 4].[2]
| Key study | Design | Microbiome shift | Clinical impact |
|---|---|---|---|
| Piloquet et al. 2024[29] | DB-RCT, 321 infants; formula with 5-HMO blend+B. infantis LMG11588 and B. lactis | Faecal pH 5.3 versus 6.2; bifidobacteria dominance within 2 weeks | 42% fewer diarrhoea episodes |
| Sheng et al. 2025[30] | RCT, 160 infants; organic formula+GOS/FOS+Limosilactobacillus reuteri/Lactobacillus reuteri and B. infantis | SCFAs, secretory IgA | Lower CRP and eczema incidence by 6 months |
| Chew et al. 2024[31] | Toddler formula with scGOS/lcFOS+B. breve M-16V | Restored Bacteroidota in C-section infants | Better iron status (Hb+0.6 g/dL) |
FOS: Fructo-oligosaccharides, GOS: Galacto-oligosaccharides, HMOs: Human milk oligosaccharides, Hb: Haemoglobin, DB-RCT: Double-blind randomised controlled trial, RCT: Randomised controlled trial, B. infantis: Bifidobacterium infantis, CRP: C-reactive protein, Hb: Haemoglobin, SCFAs: Short chain fatty acids
The gut-bone axis highlights the gut microbiome’s role in bone health. Gut bacteria influence bone growth and development through immune modulation and bioactive metabolite production. SCFAs, particularly butyrate, lower gut pH, thereby enhancing calcium and phosphorus absorption, which is essential for bone mineralisation. By modulating osteoblast and osteoclast activity, as well as affecting mineral absorption, the gut microbiome significantly influences bone matrix formation and overall bone health.[11]
PRACTICAL RECOMMENDATIONS FOR PAEDIATRICIANS
Promote breastfeeding
Exclusive breastfeeding for 6 months fosters a healthy gut microbiome, supporting immunity, bone health, brain development and social growth.
Support gut health
Guide parents on making informed feeding choices to maintain microbial balance, support digestion, immunity, and neurodevelopment in the first 2–3 years of life. In the absence of breastfeeding, advise parents to choose the appropriate feeding option and avoid cow’s milk, as this would promote optimal digestion, immunity and neurodevelopment.
Strategies to prevent gut dysbiosis: Implement targeted approaches to reduce the risk of FGIDs and microbiome imbalances
Probiotics: L. reuteri for colic relief and gut microbiome modulation during the first 12 months of life to reduce the risk of FGIDs such as colic, diarrhoea and constipation. Saccharomyces boulardii for diarrhoea prevention
Pre-biotics: Recommend pre-biotic-enriched formulas for non-breastfed infants to support a beneficial microbial composition. For non-breastfed infants, suggest formulas containing pre-biotics along with the probiotics that help colonise. For example, GOS enhances the colonisation of L. reuteri, supporting a healthy microbial balance
Diet and lifestyle: Encourage practices that sustain microbial diversity and prevent dysbiosis-related health concerns.
Recent randomised-controlled trials (RCTs), network meta-analyses and mechanistic studies confirm that targeted pre-, pro-, syn- and post-biotics can steer the infant gut microbiome towards a breast-milk-like, bifidobacteria-rich state; raise SCFA output; tighten epithelial junctions and lower rates of necrotising enterocolitis (NEC), infectious diarrhoea, regurgitation and even early eczema.
EMERGING RESEARCH DIRECTIONS
Personalised microbiome interventions: Tailored use of probiotics, pre-biotics, synbiotics and post-biotics optimises gut health, immunity and metabolism, helping prevent gut dysbiosis, FGIDs and atopic conditions.[36]
Post-biotics and para-biotics: Stable, safer alternatives to probiotics with immunomodulatory and anti-inflammatory benefits, useful in NEC, colic, diarrhoea and allergies, especially for neonates and immunocompromised children [Table 5].[32]
| Key evidence | Description | Main finding |
|---|---|---|
| Wegh et al. review 2019[32] | Survey of 48 paediatric post-biotic studies | Non-viable preparations modulate cytokines and enhance barrier proteins without sepsis risk |
| Lievin-Le Moal et al. 2007[33] | RCT, 95 infants with non-rotavirus diarrhoea; lyophilised heat-killed Lactobacillus acidophilus LB | Recovery shortened by 24 h versus live-culture control |
| Rattanaprasert et al. 2014[8] | In vitro +human persistence study of Limosilactobacillus reuteri/Lactobacillus reuteri with GOS | Heat-treated supernatant still inhibited pathogens and supported tight-junction gene expression. |
| Liu et al. 2023[34] | Post-biotic derived from heat-treated Lactobacillus LB in adult volunteers | Stool butyrate, claudin-1 mRNA, and no adverse events |
| Tonon et al. 2021[35] | AR-formula with scGOS/lcFOS+post-biotic fermentate | 35% greater reduction in regurgitation frequency versus the control formula |
RCT: Randomised controlled trial, GOS: Galacto-oligosaccharides, LB: Lactobacillus, mRNA: messenger Ribo nucleic acid
Next-gen synbiotics: Strain-specific formulations combining probiotics, pre-biotics and post-biotics to enhance gut health, nutrient absorption and immunity, particularly in high-risk infants and children.[37]
CONCLUSION
Achieving and maintaining gut health is a key indicator of overall health, as the gut has become established as a central organ that influences various other bodily systems. Early gut microbiome development plays a crucial role in ensuring lifelong health. Pre-biotics fuel beneficial bacteria through the production of SCFAs, while probiotics help restore balance, supporting digestion, immunity and resilience against diseases.
Paediatricians should advocate for breastfeeding and educate families on gut-friendly diets. The key gut-related axes such as the gut-bone, gut-brain and gut-immunity axes emphasise the importance of early strategies to maintain eubiosis and promote long-term well-being. In cases where breastfeeding is not possible, paediatricians should guide families in selecting appropriate feeding options to support gut health.
Ethical approval:
Institutional review board approval is not required.
Declaration of patient consent:
Patient’s consent is not required as there are no patients in this study.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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