Reduced microbial diversity in human intestines has been implicated in various conditions such as diabetes, colorectal cancer, and inflammatory bowel disease. The role of physical fitness in the context of human intestinal microbiota is currently not known. We used high-throughput sequencing to analyze fecal microbiota of 39 healthy participants with similar age, BMI, and diets but with varying cardiorespiratory fitness levels. Fecal short-chain fatty acids were analyzed using gas chromatography. We showed that peak oxygen uptake (VO2peak), the gold standard measure of cardiorespiratory fitness, can account for more than 20 % of the variation in taxonomic richness, after accounting for all other factors, including diet. While VO2peak did not explain variation in beta diversity, it did play a significant role in explaining variation in the microbiomes’ predicted metagenomic functions, aligning positively with genes related to bacterial chemotaxis, motility, and fatty acid biosynthesis. These predicted functions were supported by measured increases in production of fecal butyrate, a short-chain fatty acid associated with improved gut health, amongst physically fit participants. We also identified increased abundances of key butyrate-producing taxa (Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae) amongst these individuals, which likely contributed to the observed increases in butyrate levels. Results from this study show that cardiorespiratory fitness is correlated with increased microbial diversity in healthy humans and that the associated changes are anchored around a set of functional cores rather than specific taxa. The microbial profiles of fit individuals favor the production of butyrate. As increased microbiota diversity and butyrate production is associated with overall host health, our findings warrant the use of exercise prescription as an adjuvant therapy in combating dysbiosis-associated diseases.

The dynamics of the tripartite relationship between the host, gut bacteria and diet in the gut is relatively unknown. An imbalance between harmful and protective gut bacteria, termed dysbiosis, has been linked to many diseases and has most often been attributed to high-fat dietary intake. However, we recently clarified that the type of fat, not calories, were important in the development of murine colitis. To further understand the host-microbe dynamic in response to dietary lipids, we fed mice isocaloric high-fat diets containing either milk fat, corn oil or olive oil and performed 16S rRNA gene sequencing of the colon microbiome and mass spectrometry-based relative quantification of the colonic metaproteome. The corn oil diet, rich in omega-6 polyunsaturated fatty acids, increased the potential for pathobiont survival and invasion in an inflamed, oxidized and damaged gut while saturated fatty acids promoted compensatory inflammatory responses involved in tissue healing. We conclude that various lipids uniquely alter the host-microbe interaction in the gut. While high-fat consumption has a distinct impact on the gut microbiota, the type of fatty acids alters the relative microbial abundances and predicted functions. These results support that the type of fat are key to understanding the biological effects of high-fat diets on gut health.

The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs’ persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic mice treated with either BioPersist or BioColoniz as compared to their unmodified parent strains (Escherichia coli Nissle 1917 [EcN] and Lactobacillus reuteri, respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.