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Infant Gut Microbiome Study Highlights Development, Rhythmicity Over Time

NEW YORK – New research suggests that the establishment of infant gut microbial communities over time, including the advent of daily gut microbial community fluctuations, is largely independent of the type of diet an infant consumes. In contrast, the work uncovered significant differences in fecal metabolite profiles that did track with diet.

"The infant microbiome gradually develops toward a more diverse adult-like microbiome over time," Dirk Haller, a nutrition and immunology researcher affiliated with the Technical University of Munich, and his colleagues wrote in a study published in Cell Host and Microbe on Tuesday.

As part of a randomized controlled clinical trial in Germany, Haller and colleagues collected almost 1,000 stool samples from 210 infants over their first year of life, using 16S ribosomal RNA gene sequencing and shallow metagenomic sequencing to profile gut bacterial community composition and gene content in stool samples collected over time at specified times of day.

From there, they were able to compare fecal gut microbe and metabolite patterns at 2 weeks, 1 month, 3 months, 7 months, 12 months, and 24 months of age in infants who were breastfed or fed using formula with or without galacto-oligosaccharide (GOS) sugars or breast milk-derived bifidobacteria supplementation, alone, or in combination.

"Exclusively breastfed infants served as a reference group to evaluate the impact of infant formula feeding," the authors explained.

To that, the team further added untargeted metabolomic data generated with ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry on fecal, formula, and breast milk samples.

Although the team did see subtle diet-related differences in gut microbial community composition between infants — including an uptick in Bifidobacterium species B. longum and B. breve in samples from infants receiving GOS-supplemented formula — the overall gut microbiome patterns were largely comparable across diet in infants who were the same age.

"When we compared breastfed and formula-fed infants, the differences in microbiome colonization were marginal," Haller said in a statement. Such results suggested that the human intestinal system "is probably a little bit more flexible in adapting to what the environment has to offer," he added.

In particular, the results pointed to an age-related rise in bacterial richness and diversity, along with enhanced representation by bifidobacterial species in older infants.

Despite the presence of diet-associated metabolite patterns, meanwhile, the investigators were able to identify 24-hour oscillations in both bacterial composition and metabolite profiles in infant fecal samples collected at different times of day across the dietary groups.

Together, such results suggested that "circadian regulation starts at the early stages of life," they wrote, "with possible functional contribution to the infant microbiome."

The team went on to confirm the daily rhythmicity of dominant taxa isolated from infant gut samples in a chemostat model used to grow the bugs in the lab, supporting the notion that the infant gut microbes follow a circadian cycle that develops as the children age.

The study's authors suggested that such findings point to the "need for further analysis of circadian fluctuations of both bacteria and metabolites and their functional role in contributing to the benefits of infant nutrition."