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Environmental and Maternal Imprints on Infant Gut Metabolic Programming

Kine Eide Kvitne, Celeste Allaband, Jennifer C. Onuora, Daniela Perry, Simone Zuffa, Lucas Patel, Vincent Charron-Lamoureux, Ipsita Mohanty, Kristija Sejane, Abubaker Patan, Abdullah Al Mahmud, Tahmeed Ahmed, Diego G. Bassani, Antonio González, Davidson H. Hamer, Rashidul Haque, Benjamin Ho, Md Iqbal Hossain, Mohammad Shahidul Islam, Daniel McDonald, Lisa G. Pell, Huma Qamar, Daniel E. Roth, Samir Saha, Prakesh S. Shah, Md Muniruzzaman Siddiqui, Shafiqul Alam Sarker, Shamima Sultana, Sydney Thomas, Lindsey A. Burnett, Shirley M. Tsunoda, Lars Bode, Pieter C. Dorrestein, Rob Knight

Posted on: 26 October 2025 , updated on: 28 October 2025

Preprint posted on 24 July 2025

Delivery mode, water treatment and milk composition shape the microbiome and metabolome during the first six months of life.

Selected by Siddharth Singh

Early-life nutrition and microbiome development are deeply intertwined, but most studies focus on high-income populations. In a new preprint, Kvitne and team address this gap by profiling the microbiome and metabolome of 55 Bangladeshi mother-infant pairs during the first six months of life. This systems-level, longitudinal approach reveals how maternal inputs and local environment jointly shape the infant gut metabolome.

Why I Highlight This Work

Early infancy is a critical window for immune and metabolic development, and the infant gut microbiome plays a key role in this process. However, most microbiome and metabolome studies focus on high-income countries, while low-resource settings are understudied. Kvitne et al. (2025) address this gap by profiling infants’ microbiome and metabolome in a low-income context. In their preprint, the authors used a systems-biology approach to understand how maternal and environmental factors jointly shape the infant gut ecosystem. They followed 55 mother-infant pairs in Dhaka, Bangladesh, over the first six months of life, collecting longitudinal fecal samples (from infants and mothers) and breast milk. They then combined high-throughput microbiome sequencing with untargeted metabolomics, tracking how gut microbial composition and metabolic profiles co-evolve (Fig. 1).

Figure 1: Rapid shifts and unique key metabolic signals. Followed 55 mother-infant pairs in Dhaka, Bangladesh, for the first six months of life, repeatedly sampling infant stool, blood, mouth, and skin, plus mothers’ stool, milk, and a vaginal swab, and ran untargeted metabolomics and metagenomics. Preprint figure made available under a CC-BY 4.0 International license.

Key findings

The multi-omics analysis revealed several intriguing patterns about how the baby’s gut metabolism matures:

One striking finding is that stools show rising levels of bacteria-derived lipids as infants age. In particular, microbial metabolites like bile acid amidates and short-chain N-acyl lipids consistently increase over time. Bile acids are host-produced molecules that gut bacteria frequently modify by deconjugating taurine or forming new amide bonds. The authors found that these complex bile conjugates rise hand-in-hand with higher levels of the bacterial bile salt hydrolase (bsh) gene, indicating active microbial processing of bile acids.

Kvitne and team also highlight contrasting maternal versus environmental influences. Microbial source-tracking confirmed that many infant gut bacteria are seeded from the mother’s feces, but a substantial fraction comes from the wider environment. This dual sourcing is reflected in the metabolites, too. Infants born via C-section or given untreated water show distinct metabolic profiles. Specifically, C-section delivery and lack of water treatment were linked to transient metabolic shifts, including increases in bile amidates, N-acyl lipids, and acylcarnitines.

The study uses an integrative multi-omics analysis to connect microbes and metabolites. By correlating the abundance of specific bacteria with metabolite levels, the authors identify microbe-metabolite pairs that explain the observed patterns. This co-metabolism analysis shows that the evolving gut community directly contributes to the emerging metabolic landscape. The infant gut resembles an ecosystem where host biology and microbes co-adapt to shape metabolic development.

Significance

This work provides a compelling systems-biology view of host-microbiome co-development in early life. Extending multi-omics profiling to a low-resource setting reveals that non-genetic factors, from maternal milk to sanitation, can profoundly steer the metabolic maturation of infants. Understanding these patterns has important implications for global child health; such insights could inform interventions. Future studies can build on these findings to link specific metabolic trajectories with long-term growth or immune outcomes. Kvitne and colleagues offer a rich dataset showing that a co-evolutionary interplay of mother and environment programs an infant’s gut. This is a vivid example of how systems biology can unravel complex early-life interactions.

Questions for the authors

  1. How do stool bile amidates and N-acyl lipids map onto infant serum bile-acid profiles and receptor activity, such as FXR or TGR5, and do immune or endocrine markers co-vary?
  2. Can effects attributed to Cesarean delivery be separated from peripartum antibiotic exposure by timing and dose, and does this account for the transient nature of the metabolic shift?
  3. Could a compact panel of 5 to 10 metabolites function as a maturation clock that generalizes across households and geographies, and how stable is it to diet and season?
  4. What causal tests are next: colonization with strains that differ in bile salt hydrolase activity, human-milk-oligosaccharide supplementation stratified by maternal secretor status, or household water-treatment interventions?

Tags: bile salt hydrolase, coevolution, environmental exposures, human milk, human milk oligosaccharides, infant microbiome, metabolic programming, metabolomics, multi-omics

doi: https://doi.org/10.1242/prelights.41799

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