Structure and function of the healthy pre-adolescent pediatric gut microbiome
Emily B. HollisterKevin RiehleRuth Ann LunaErica M. WeidlerMichelle Rubio-GonzalesToni-Ann MistrettaSabeen RazaHarshaVardhan DoddapaneniGinger MetcalfDonna M. MuznyRichard A. GibbsJoseph F. PetrosinoRobert J. ShulmanJames Versalovic
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Abstract:
The gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limited. Using 16S rRNA gene and shotgun metagenomic sequencing, we characterized the structure, function, and variation of the healthy pediatric gut microbiome in a cohort of school-aged, pre-adolescent children (ages 7–12 years). We compared the healthy pediatric gut microbiome with that of healthy adults previously recruited from the same region (Houston, TX, USA). Although healthy children and adults harbored similar numbers of taxa and functional genes, their composition and functional potential differed significantly. Children were enriched in Bifidobacterium spp., Faecalibacterium spp., and members of the Lachnospiraceae, while adults harbored greater abundances of Bacteroides spp. From a functional perspective, significant differences were detected with respect to the relative abundances of genes involved in vitamin synthesis, amino acid degradation, oxidative phosphorylation, and triggering mucosal inflammation. Children's gut communities were enriched in functions which may support ongoing development, while adult communities were enriched in functions associated with inflammation, obesity, and increased risk of adiposity. Previous studies suggest that the human gut microbiome is relatively stable and adult-like after the first 1 to 3 years of life. Our results suggest that the healthy pediatric gut microbiome harbors compositional and functional qualities that differ from those of healthy adults and that the gut microbiome may undergo a more prolonged development than previously suspected.Keywords:
Gut microbiome
Medical microbiology
The gut microbiome has an important role in health, and diet represents a key lever for shaping the gut microbiome across all stages of life. Maternal milk consumption in neonates leads to long-term health effects, indicating that pliability in the infant gut microbiome in response to diet can drive enduring change. The ability of diet to drive lasting changes in the adult gut microbiome is less understood. We studied the effect of an extreme dietary shift on the fecal microbiome of 46 Labrador retriever dogs (mean age, 4.6 years) over 11 months. Dogs were fed a nutritionally complete, commercially available complex diet (CD) for a minimum of 5 weeks, followed by highly purified diets (PDs) for 36 weeks, and the initial CD for at least a further 4 weeks. Fecal samples were collected at regular intervals for DNA extraction. By analyzing 16S rRNA genes and the metagenomes, we observed minor effects on microbial diversity but significant changes in bacterial taxa and genetic potential when a PD was fed. Specifically, metagenomics identified an enrichment of quinone- and GABA-related pathways on PD, providing insights into dietary effects on cross-feeding strategies impacting community structure. When dogs returned to the CD, no significant differences were found with the initial time point. These findings are consistent with the gut microbiome being rapidly adaptable but capable of being reconstituted when provided with similar diets. These data highlight that long-term changes in the adult dog gut microbiome may only be achieved through long-term maintenance on a specified diet, rather than through feeding a transitionary diet.IMPORTANCE Diet can influence the adult gut microbiome (the community of bacteria) and health outcomes, but the ability to make changes persisting beyond feeding of a particular diet is poorly understood. We investigated whether feeding highly purified diets to adult dogs for 36 weeks would alter bacterial populations sufficiently to result in a persistent change following the dogs' return to a commercial diet. As expected, the microbiome changed when the purified diet was fed, but the original microbiome was reconstituted within weeks of the dogs returning to the commercial diet. The significance of these findings is in identifying an intrinsic stability of the host microbiome in healthy dogs, suggesting that dietary changes to support adult dog health through modifying the gut microbiome may be achieved only through maintenance on a specified diet, rather than through feeding transitionary diets.
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The dramatic increase of chronic diseases in industrialized societies might be driven in part by a disruption of gut microbiome composition and function (e.g., reduced fiber fermentation) and impaired intestinal barrier integrity. We developed a microbiome restoration strategy based on a diet that resembles key aspects of a non-industrialized diet (Non-Ind) and a probiotic Limosilactobacillus reuteri (a species rarely found in microbiome from industrialized populations). Using a randomized controlled pilot study, 30 participants consumed either the Non-Ind diet or their usual diet in a crossover fashion for three weeks each. Participants were also divided into three groups and consumed either a single dose of one of two Lm. reuteri strains or a placebo on day four of each diet period. The Non-Ind diet enhanced the temporal persistence of one of the Lm. reuteri strains, but had no measurable effects on microbiome and host. In contrast, the Non-Ind diet shifted overall fecal microbiome composition (R2=0.015, p=0.001; ADONIS), and significantly altered 56% of Amplicon Sequence Variants obtained from 16S dataset (FDR lower than 0.05), 22% of species-level genome bins, and 21% of metabolic pathways obtained from metagenomic dataset (FDR lower than 0.05). Bacteria fermentation was enhanced, exhibited by increased concentration of total fecal short-chain fatty acids (+10.7%, p=0.03) and reduced fecal pH (-3.8%, p=0.002). Furthermore, we observed reductions in six chronic disease risk markers (all p lower than 0.01): total cholesterol (-14.1%), low-density lipoprotein cholesterol (-16.8%), high-density lipoprotein (HDL) cholesterol (-11.3%), non-HDL cholesterol (-15.2%), glucose (-6.3%), and C-reactive protein (-14.2%). The diet also reduced fecal calprotectin (-21.0%, p=0.002) and zonulin levels (-14.9%, p=0.025) that are markers of gut inflammation and impaired barrier functions, respectively. Our study demonstrates pronounced beneficial effects of a microbiome restoration strategy based on the Non-Ind diet on metabolic markers of health. The findings provide valuable information for improving human health in modern societies. Ongoing analyses are exploring the mechanistic links between diet-induced changes in the gut microbiome and the physiological effects on the host.
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Background Humans and animals living in close proximity may share microbiome constituents at the household level because of daily domestic contact. Such sharing could affect enteric and metabolic functions of the gut microbiome of humans and livestock living in such households. We sought to characterise the microbiome of children, cattle, chickens, and environmental surfaces within households in western Kenya to determine the degree of microbiome sharing.
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The increasing prevalence and severity of pediatric food allergies (FA) demands innovative preventive and therapeutic strategies. Emerging evidence suggests a pivotal role for the gut microbiome in modulating susceptibility to FA. Studies have demonstrated that alteration of gut microbiome could precede FA, and that particular microbial community structures early in life could influence also the disease course. The identification of gut microbiome features in pediatric FA patients is driving new prevention and treatment approaches. This review is focused on the potential role of the gut microbiome as a target for FA prevention and treatment.
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