Probiotics are increasingly used by consumers and practitioners to reduce gastrointestinal (GI) distress and improve gut function. Here, we sought to determine whether the addition of supplemental bacteriophages (PreforPro) could enhance the effects of a common probiotic, Bifidobacterium animalis subsp. lactis (B. lactis) on GI health. A total of 68 participants were enrolled in a 4-week, randomized, parallel-arm, double-blind, placebo-controlled trial where primary outcomes included self-assessments of GI health, a daily stool log, and 16s rRNA analysis of gut microbial populations. We observed within-group improvements in GI inflammation (p = 0.01) and a trending improvement in colon pain (p = 0.08) in individuals consuming B. lactis with PreforPro, but not in the group consuming only the probiotic. There was also a larger increase in Lactobacillus and short-chain fatty acid-producing microbial taxa detected in the stool of participants taking PreforPro with B. lactis compared to the probiotic alone. Overall, these results suggest the addition of PreforPro as a combination therapy may alter gut ecology to extend the GI benefits of consuming B. lactis or other probiotics.

The gut microbiota has been shown to mediate host health. Emerging data implicate gut microbial metabolites of tryptophan metabolism as potential important mediators. We examined the effects of indole-3-propionic acid in Western diet-fed mice and found no beneficial cardiometabolic effects. Our data do not support the supposition that indole-3-propionic acid (IPA) mediates beneficial metabolic effects downstream of the gut microbiota and may be potentially deleterious in higher circulating levels.

Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals.We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free.These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiotatargeted therapies in the prevention or treatment of cardiovascular disease.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain-specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a pilot randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-intervention, as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an increase in anti-inflammatory immune cell populations in response to ex vivo LPS stimulation of PBMCs in the DE111 intervention group. Overall perceived gastrointestinal health, microbiota, and circulating and fecal markers of inflammation (Il-6, sIgA) and gut barrier function (plasma zonulin) were largely unaffected by DE111 intervention, although the study may have been underpowered to detect these differences. These pilot data provide information and justification to conduct an appropriately powered clinical study to further examine the immunomodulatory potential of B. subtilis DE111 in human populations.

Objectives The gut microbiota is emerging as an important regulator of cardiovascular health. Indeed, gut dysbiosis is increasingly being linked to the development of cardiovascular disease (CVD). Aging and obesity are associated with the development of CVD largely due to the development of vascular dysfunction, namely endothelial dysfunction and arterial stiffness. The objective of this study was to examine the relationship between the gut microbiota, blood pressure, and vascular function in aging overweight and obese individuals. Methods This cross-sectional study included fifteen overweight and obese (mean body mass index, BMI: 29.5; range: 25.8–37.0) middle-aged/older men and postmenopausal women (mean age: 53; range: 42–64 years). Blood pressure, arterial stiffness (augmentation index, AIx, and aortic pulse wave velocity, aPWV), and endothelial function (reactive hyperemia index, RHI) were assessed. Stool samples were collected for gut microbiota analysis using 16S ribosomal RNA sequencing. Principal coordinates analysis and Pearson's correlations were performed to evaluate the relationship between the gut microbiota and measures of vascular function and blood pressure. Results Global gut microbiota phenotypes clustered most strongly by aPWV (groups separated by median value) as visualized by Non-Metric Dimensional Scaling plot of Bray-Curtis Distances (stress = 0.09; P = 0.07). Several bacterial taxa correlated with vascular parameters. For example, Bifidobacterium longum (r = 0.80, P < 0.001) and Akkermansia muciniphila (r = 0.56, P = 0.047) were positively correlated with RHI. Bifdobacterium bifidum (r = −0.61, P = 0.02) and Oxalobacter formigenes (r = −0.62, P = 0.02) were negatively correlated with systolic blood pressure. Interestingly, there was no significant clustering by BMI groupings (overweight vs. obese) or correlations between BMI and specific taxa. Conclusions These preliminary data suggest that the gut microbiota is linked to vascular dysfunction and increased blood pressure in aging overweight and obese individuals independent of BMI. Further data collection and analysis are currently underway to explore these relationships in a larger human cohort, and to explore underlying mechanisms through transferring of vascular phenotypes in humans to germ-free mice through microbiota transplantation. Funding Sources NIFA, USDA.