Reduced alcohol preference and intake after fecal transplant in patients with alcohol use disorder is transmissible to germ-free mice

• Published in: Nature communications Vol. 13; no. 1; pp. 6198 - 14
• Main Authors: Wolstenholme, Jennifer T., Saunders, Justin M., Smith, Maren, Kang, Jason D., Hylemon, Phillip B., González-Maeso, Javier, Fagan, Andrew, Zhao, Derrick, Sikaroodi, Masoumeh, Herzog, Jeremy, Shamsaddini, Amirhossein, Peña-Rodríguez, Marcela, Su, Lianyong, Tai, Yun-Ling, Zheng, Jing, Cheng, Po-Cheng, Sartor, R. Balfour, Gillevet, Patrick M., Zhou, Huiping, Bajaj, Jasmohan S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 49/91; 64/60; 692/4020/2741/2135; 692/4020/4021/1607/1604; 692/4020/4021/1607/1608; Acceptance; Alcohol Drinking; Alcohol use; Alcoholic beverages; Alcoholism - therapy; Alcohols; Animal models; Animals; Cell proliferation; Cellular stress response; Cirrhosis; Clinical trials; Digestive system; Digestive tract; Epithelial cells; Epithelium; Ethanol; Fecal Microbiota Transplantation; Fecal microflora; Feces; Germfree; Humanities and Social Sciences; Humans; Immune response; Intestinal microflora; Intestine; Liver; Liver cirrhosis; Liver diseases; Male; Mice; Mice, Inbred C57BL; Microbiota; Microorganisms; Morbidity; multidisciplinary; Oxidative stress; Patients; Phenotypes; Prefrontal cortex; Science; Science (multidisciplinary); Transplantation; Transplants & implants
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34054-6

Alcohol use disorder is a major cause of morbidity, which requires newer treatment approaches. We previously showed in a randomized clinical trial that alcohol craving and consumption reduces after fecal transplantation. Here, to determine if this could be transmitted through microbial transfer, germ-free male C57BL/6 mice received stool or sterile supernatants collected from the trial participants pre-/post-fecal transplant. We found that mice colonized with post-fecal transplant stool but not supernatants reduced ethanol acceptance, intake and preference versus pre-fecal transplant colonized mice. Microbial taxa that were higher in post-fecal transplant humans were also associated with lower murine alcohol intake and preference. A majority of the differentially expressed genes (immune response, inflammation, oxidative stress response, and epithelial cell proliferation) occurred in the intestine rather than the liver and prefrontal cortex. These findings suggest a potential for therapeutically targeting gut microbiota and the microbial-intestinal interface to alter gut-liver-brain axis and reduce alcohol consumption in humans. Gut microbiota composition is altered in patients with alcohol use disorder, and fecal microbiota transplant reduced alcohol craving in patients with alcohol use disorder and liver cirrhosis in a phase 1 clinical trial. Here the authors used stool samples collected in the trial to report that this phenotype is transmissible via microbial transfer to germ free mice, as assessed by reduced ethanol acceptance, intake and preference.