Targeting keystone species helps restore the dysbiosis of butyrate‐producing bacteria in nonalcoholic fatty liver disease
Dingfeng Wu,
Lei Liu,
Na Jiao,
Yida Zhang,
Li Yang,
Chuan Tian,
Ping Lan,
Lixin Zhu,
Rohit Loomba,
Ruixin Zhu
Affiliations
Dingfeng Wu
National Clinical Research Center for Child Health, The Children's Hospital Zhejiang University School of Medicine Hangzhou Zhejiang People's Republic of China
Lei Liu
The Shanghai Tenth People's Hospital, School of Life Sciences and Technology Tongji University Shanghai People's Republic of China
Na Jiao
National Clinical Research Center for Child Health, The Children's Hospital Zhejiang University School of Medicine Hangzhou Zhejiang People's Republic of China
Yida Zhang
Department of Biomedical Informatics Harvard Medical School Boston Massachusetts USA
Li Yang
State Key Laboratory of Biotherapy, West China Hospital Sichuan University and Collaborative Innovation Center Chengdu Sichuan People's Republic of China
Chuan Tian
The Shanghai Tenth People's Hospital, School of Life Sciences and Technology Tongji University Shanghai People's Republic of China
Ping Lan
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Guangdong Institute of Gastroenterology Sun Yat‐sen University Guangzhou People's Republic of China
Lixin Zhu
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Guangdong Institute of Gastroenterology Sun Yat‐sen University Guangzhou People's Republic of China
Rohit Loomba
Department of Medicine, Division of Gastroenterology and Epidemiology, NAFLD Research Center University of California San Diego La Jolla California USA
Ruixin Zhu
The Shanghai Tenth People's Hospital, School of Life Sciences and Technology Tongji University Shanghai People's Republic of China
Abstract The dysbiosis of the gut microbiome is one of the pathogenic factors of nonalcoholic fatty liver disease (NAFLD) and also affects the treatment and intervention of NAFLD. Among gut microbiomes, keystone species that regulate the integrity and stability of an ecological community have become the potential intervention targets for NAFLD. Here, we collected stool samples from 22 patients with nonalcoholic steatohepatitis (NASH), 25 obese patients, and 16 healthy individuals from New York for 16S rRNA gene sequencing. An algorithm was implemented to identify keystone species based on causal inference theories and dynamic intervention simulation. External validation was performed in an independent cohort from California. Eight keystone species in the gut of NAFLD, represented by Porphyromonas loveana, Alistipes indistinctus, and Dialister pneumosintes, were identified, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome with 92.3% recovery. These keystone species regulate intestinal amino acid metabolism and acid–base environment to promote the growth of the butyrate‐producing Lachnospiraceae and Ruminococcaceae species that are significantly reduced in NAFLD patients. Our findings demonstrate the importance of keystone species in restoring the microbial composition toward a normal gut microbiome, suggesting a novel potential microbial treatment for NAFLD.
