Reduced alcohol preference and intake after fecal transplant in patients with alcohol use disorder is transmissible to germ-free mice
Jennifer T. Wolstenholme, Justin M. Saunders, Maren L. Smith, Jason D. Kang, Phillip B. Hylemon, Javier González‐Maeso, Andrew Fagan, Derrick Zhao, Masoumeh Sikaroodi, Jeremy Herzog, Amirhossein Shamsaddini, Marcela Peña‐Rodríguez, Lianyong Su, Yunling Tai, Jing Zheng, Po-Cheng Cheng, R. Balfour Sartor, Patrick M. Gillevet, Huiping Zhou, Jasmohan S. Bajaj
Abstract
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.