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 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, Yun-Ling Tai, Jing Zheng, Po-Cheng Cheng, R. Balfour Sartor, Patrick M. Gillevet, Huiping Zhou and Jasmohan S. Bajaj ()
Additional contact information
Jennifer T. Wolstenholme: Virginia Commonwealth University
Justin M. Saunders: Virginia Commonwealth University
Maren Smith: Virginia Commonwealth University
Jason D. Kang: Virginia Commonwealth University
Phillip B. Hylemon: Virginia Commonwealth University
Javier González-Maeso: Virginia Commonwealth University
Andrew Fagan: Virginia Commonwealth University and Richmond VA Medical Center
Derrick Zhao: Virginia Commonwealth University
Masoumeh Sikaroodi: George Mason University
Jeremy Herzog: University of North Carolina at Chapel Hill
Amirhossein Shamsaddini: George Mason University
Marcela Peña-Rodríguez: University of Guadalajara
Lianyong Su: Virginia Commonwealth University
Yun-Ling Tai: Virginia Commonwealth University
Jing Zheng: Virginia Commonwealth University
Po-Cheng Cheng: Virginia Commonwealth University
R. Balfour Sartor: University of North Carolina at Chapel Hill
Patrick M. Gillevet: George Mason University
Huiping Zhou: Virginia Commonwealth University
Jasmohan S. Bajaj: Virginia Commonwealth University and Richmond VA Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34054-6

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