Opioid agonist and antagonist use and the gut microbiota: associations among people in addiction treatment.

Murine models suggest that opioids alter the gut microbiota, which may impact opioid tolerance and psychopathology. We examined how gut microbiota characteristics related to use of opioid agonists and antagonists among people receiving outpatient addiction treatment. Patients (n = 46) collected stool samples and were grouped by use of opioid agonists (heroin, prescription opioids), antagonists (naltrexone), agonist-antagonist combinations (buprenorphine-naloxone), or neither agonists nor antagonists within the month before enrollment. We sequenced the V4 region of the 16S rRNA gene using Illumina MiSeq to examine how alpha diversity, enterotypes, and relative abundance of bacterial genera varied by opioid agonist and antagonist exposures. Compared to 31 participants who used neither agonists nor antagonists, 5 participants who used opioid agonists (without antagonists) had lower microbiota diversity, Bacteroides enterotypes, and lower relative abundance of Roseburia, a butyrate producing genus, and Bilophila, a bile acid metabolizing genus. There were no differences in gut microbiota features between those using agonist + antagonists (n = 4), antagonists only (n = 6), and neither agonists nor antagonists. Similar to murine morphine exposure models, opioid agonist use was associated with lower microbiota diversity. Lower abundance of Roseburia and Bilophila may relate to the gut inflammation/permeability and dysregulated bile acid metabolism observed in opioid-exposed mice.

Diet rapidly and reproducibly alters the human gut microbiome.

Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice.

The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(−/−), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(−/−) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.

[Bilophila wadsworthia isolated from surgical specimens].

Bilophila wadsworthia is a recently recognized nonspore-forming anaerobic Gram-negative rod and is reported to be associated with various surgical infections. In the present study, the isolation rate of B. wadsworthia from surgical specimens and its antimicrobial susceptibilities were examined. Last 5 years, B. wadsworthia was isolated from 46 (5.2%) out of 884 specimens from the surgical abdominal infections. B. wadsworthia was most frequently isolated from secondary peritonitis such as perforated peritonitis, followed by postoperative peritonitis. There is no case of single isolation of B. wadsworthia. The rate of mixed infection with Bacteroides spp. (24.8%) was highest, followed by Escherichia coli (11.6%) and Enterococcus spp. (10.1%). Although B. wadsworthia was highly resistant to many beta-lactam antibiotics, clindamycin showed strongest activities with MIC90 of 1 microg/mL, followed by minocycline and ciprofloxacin with 4micro g/mL, and levofloxacin with 8 microg/mL, respectively.