Biology subjects

Holmes, Z. C.

Publications and source records attributed to Holmes, Z. C..

5 recordsLinked to original sources

bioRxiv2024

Interplay between particle size and microbial ecology in the gut microbiome

Physical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Surprisingly, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that mammalian and human gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally, ex vivo culture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion, and that the microbiomes of individuals vary in this capacity. These new insights also suggest FPS in humans to be governed by processes beyond those found in other mammals and emphasize the importance of gut microbiota in shaping their own abiotic environment.

microbiology↗

bioRxiv2021

Microbiota responses to different prebiotics are conserved within individuals and associated with habitual fiber intake

BackgroundShort-chain fatty acids (SCFAs) derived from gut bacteria are associated with protective roles in diseases ranging from obesity to colorectal cancers. Intake of microbially accessible dietary fibers (prebiotics) lead to varying effects on SCFA production in human studies, and gut microbial responses to nutritional interventions vary by individual. It is therefore possible that prebiotic therapies will require customizing to individuals. ResultsHere, we explored prebiotic personalization by conducting a three-way crossover study of three prebiotic treatments in healthy adults. We found that within individuals, metabolic responses were correlated across the three prebiotics. Individual identity, rather than prebiotic choice, was also the major determinant of SCFA response. Across individuals, prebiotic response was inversely related to basal fecal SCFA concentration, which, in turn, was associated with habitual fiber intake. Experimental measures of gut microbial SCFA production for each participant also negatively correlated with fiber consumption, supporting a model in which individuals gut microbiota are limited in their overall capacity to produce fecal SCFAs from fiber. ConclusionsOur findings support developing personalized prebiotic regimens that focus on selecting individuals who stand to benefit, and that such individuals are likely to be deficient in fiber intake.

microbiology↗

bioRxiv2021

Ecological memory of prior nutrient exposure in the human gut microbiome

Many ecosystems retain an ecological memory of past conditions that affects responses to future stimuli. However, it remains unknown what mechanisms and dynamics may govern such a memory in microbial communities. Here, in both a human dietary intervention cohort and an artificial gut, we show that the human gut microbiome encodes a memory of past carbohydrate exposures. Changes in the relative abundance of primary degraders were sufficient to enhance metabolism, and these changes were mediated by transcriptional changes within hours of initial exposure. We further found that ecological memory of one carbohydrate species impacted metabolism of others. These findings demonstrate that the human gut microbiomes metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient. One Sentence SummaryRecent nutrient exposures are encoded into the structure and activity of human gut microbial communities, which enables more efficient future metabolic responses.

ecology↗

bioRxiv2020

Conserved anti-inflammatory effects and sensing of butyrate in zebrafish

Short chain fatty acids (SCFAs) are produced by microbial fermentation of dietary fiber in the gut. Butyrate is a particularly important SCFA with anti-inflammatory properties and is generally present at lower levels in inflammatory diseases associated with gut microbiota dysbiosis in mammals. We aimed to determine if SCFAs are produced by the zebrafish microbiome and if SCFAs exert conserved effects on zebrafish immunity as an example of the non-mammalian vertebrate immune system. We demonstrate that bacterial communities from adult zebrafish intestines synthesize all three main SCFA in vitro, although SCFA were below our detectable limits in zebrafish intestines in vivo. Immersion in butyrate, but not acetate or propionate, reduced the recruitment of neutrophils and M1-type pro-inflammatory macrophages to wounds. We found conservation of butyrate sensing by neutrophils via orthologs of the hydroxycarboxylic acid receptor 1 (hcar1) gene. Neutrophils from Hcar1-depeleted embryos were no longer responsive to the anti-inflammatory effects of butyrate, while macrophage sensitivity to butyrate was independent of Hcar1. Our data demonstrate conservation of anti-inflammatory butyrate effects and identify the presence of a conserved molecular receptor in fish.

immunology↗

bioRxiv2020

Short-chain fatty acid production by gut microbiota from children with obesity is linked to bacterial community composition and prebiotic choice

Pediatric obesity remains a public health burden and continues to increase in prevalence. The gut microbiota plays a causal role in obesity and is a promising therapeutic target. Specifically, the microbial production of short-chain fatty acids (SCFA) from the fermentation of otherwise indigestible dietary carbohydrates may protect against pediatric obesity and metabolic syndrome. Still, it has not been demonstrated that therapies involving microbiota-targeting carbohydrates, known as prebiotics, will enhance gut bacterial SCFA production in children and adolescents with obesity (age 10-18). Here, we used an in vitro system to examine the SCFA production by fecal microbiota from 17 children with obesity when exposed to five different commercially available over-the-counter (OTC) prebiotic supplements. We found microbiota from all 17 patients actively metabolized most prebiotics. Still, supplements varied in their acidogenic potential. Significant inter-donor variation also existed in SCFA production, which 16S rRNA sequencing supported as being associated with differences in the host microbiota composition. Last, we found that neither fecal SCFA concentration, microbiota SCFA production capacity, nor markers of obesity positively correlated with one another. Together, these in vitro findings suggest the hypothesis that OTC prebiotic supplements may be unequal in their ability to stimulate SCFA production in children and adolescents with obesity, and that the most acidogenic prebiotic may differ across individuals. IMPORTANCEPediatric obesity remains a major public health problem in the US, where 17% of children and adolescents are obese, and rates of pediatric severe obesity are increasing. Children and adolescents with obesity face higher health risks, and non-invasive therapies for pediatric obesity often have limited success. The human gut microbiome has been implicated in adult obesity, and microbiota-directed therapies can aid weight loss in adults with obesity. However, less is known about the microbiome in pediatric obesity, and microbiota-directed therapies are understudied in children and adolescents. Our research has two important findings: 1) dietary prebiotics (fiber) cause the microbiota from adolescents with obesity to produce more SCFA, and 2) the effectiveness of each prebiotic is donor-dependent. Together, these findings suggest that prebiotic supplements could help children and adolescents with obesity, but that these therapies may not be one-size-fits-all.

microbiology↗