Enterolignan-Producing Phenotypes Are Associated with Increased Gut Microbial Diversity and Altered Composition in Premenopausal Women in the United States

Abstract

Background Lignans in plant foods are metabolized by gut bacteria to the enterolignans, enterodiol (END) and enterolactone (ENL). Enterolignans have biologic activities important to the prevention of cancer and chronic diseases. We examined the composition of the gut microbial community (GMC) as a contributor to human enterolignan exposure. Methods We evaluated the association between the GMC in stool, urinary enterolignan excretion, and diet from a 3-day food record in 115 premenopausal (ages 40–45 y) women in the United States. Urinary enterolignans were measured using GC/MS. The GMC was evaluated using 454 pyrosequencing of the 16S rRNA gene. Sequences were aligned in SILVA (www.arb-silva.de). Operational taxonomic units (OTU) were identified at 97% sequence similarity. Taxonomic classification was performed and alpha and beta diversity in relationship to ENL production were assessed. Multivariate analysis and regression were used to model the association between enterolignan excretion and the GMC. Bacteria associated with ENL production were identified using univariate analysis and ridge regression. Results After adjusting for dietary fiber intake and adiposity, we found a significant positive association between ENL excretion and either the GMC (p=0.0007), or the diversity of the GMC (p=0.01). The GMC associated with high ENL production was distinct (UNIFRAC, p<0.003, MRPP) and enriched in Moryella spp., Acetanaerobacterium spp., Fastidiosipila spp., and Streptobacillus spp. Conclusion Diversity and composition of the GMC are associated with increased human exposure to enterolignans. Impact Differences in gut microbial diversity and composition explain variation in gut metabolic processes that impact environmental exposures and influences human health.

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

“…Accordingly, we previously reported that increased excretion of ENL is associated with composition and diversity of the gut microbial community. 46 Unlike plant lignan intakes, mean excretion of ENL (4.6 µmol on WG diet and 3.0 µmol on RG diet) and END (0.82 µmol on WG diet and 0.41 µmol on RG diet) of participants in our study was consistent with what has been reported previously, 47–50 although not as high as END and ENL levels obtained (9–12 µmol/24h) after ingestion of a single dose of SDG (1.3 µmol/kg body weight). 8 We did not observe a statistically significant linear association between ENL and plant lignan intakes.…”

Approved and novel strategies in diagnostics of rat bite fever and otherStreptobacillusinfections in humans and animals

“…4,13,[16][17][18][19][20][21][22] Recently, various publications suggest that Streptobacillus species might be far more common and distributed in the environment or as commensal microbiota than previously thought. 32,37,[59][60][61][62][63] It could recently be shown that the natural reservoir for the very rare cases of human S. hongkongensis infection known to date is indeed the human oropharynx à and presumably not an unidentified animal or environmental reservoir. 49 Despite a certain amount of annually published case reports, most of which have solely used 16S rRNA sequencing alone for definite diagnosis, there has not been much progress in the diagnosis of acute clinical cases of RBF in the last decades.…”

“…1). 62,63 This fuels the assumption that Streptobacillus species are far more distributed in the environment aside from their natural hosts than previously thought. Contrarily, former Streptobacillus-like organisms from fish 55 and guinea pigs [64][65][66][67] are even more distantly related to classical Streptobacillus species and indeed represent novel genera, that have been recently described.…”

Diet and Gut Microbial Function in Metabolic and Cardiovascular Disease Risk

“…The equol production phenotype was transferrable to germ-free rats: rats produced equol when they received a fecal microbiota transplant from individuals with high equol production, but not when they received a transplant from individuals with low equol production. There is a lack of data on microbial pathways for isoflavone and lignan metabolite production, but one recent study reported a positive association between gut microbiota diversity, based on 16S rRNA analysis, and enterolignan production in 115 premenopausal U.S. women[11]. …”

“…On an individual level, dietary composition contributes, at least in part, to shaping the gut microbiota through the delivery of energy for microbial growth[6–8]. In turn, gut microbiota influence the production of health-related metabolites from dietary components[9, 10], with the potential for personal variability in metabolite production based on differences in gut microbiota[11, 12]. A growing literature supports a role for gut microbiota in the development and progression of metabolic and cardiovascular disease risk[13–16], including type 2 diabetes[17–19], obesity[20–22], insulin resistance[23], inflammation[24], atherosclerosis[12, 25], hypertension[26, 27], dyslipidemia[28], and cardiovascular disease events[29, 30].…”