Punica granatum L., commonly known as the pomegranate, is an abundant source of polyphenols, including hydrolyzable ellagitannins, ellagic acid, anthocyanins, and other bioactive phytochemicals shown to be effective in defending against oxidative stress, and has immunomodulatory activities. Ellagitannins, and their hydrolyzed product ellagic acid, interact with the gut microbiota to yield secondary metabolites known as urolithins that may have health benefits. The objective of this study was to determine the effects of supplementation with a standardized punicalagin-enriched pomegranate extract, Pomella^® (250 mg), on the gut microbiome, circulating short-chain fatty acids, and gut microbial-derived ellagitannin metabolite urolithins. A randomized, double-blind, placebo-controlled study was conducted over 4 weeks on healthy volunteers aged 25–55 years. Subjects were randomly assigned to receive either an oral supplement containing 75 mg of punicalagin or an oral placebo. Stool sample collection and venipuncture were performed to analyze the gut microbiome, SCFAs, and urolithin. There was no significant change in the gut microbial diversity in both cohorts after 4 weeks of intervention, but there was a significantly increased relative abundance of Coprococcus eutectus, Roseburia faecis, Roseburia inullnivorans, Ruminococcus bicirculans, Ruminococcus calidus, and Faecalibacterium prausnitzii. Pomegranate extract (PE) supplementation led to the augmentation of circulating propionate levels (p = 0.02) and an increasing trend for acetate levels (p = 0.12). The pomegranate extract (PE) supplementation group had an increased level of circulating urolithins compared to the placebo group (6.6% vs. 1.1%, p = 0.13). PE supplementation correlated with shifts in the gut microbiome and with higher circulating levels of propionate and acetate. Further studies should explore the implications in larger cohorts and over a longer duration.

Background: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. Objectives: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. Methods: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. Results: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. Conclusions: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.