Bifidobacterium spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses
Han Li,
Jinyan Xie,
Xiuliu Guo,
Guilian Yang,
Bin Cai,
Jingtianyi Liu,
Mengjia Yue,
Yixin Tang,
Gan Wang,
Shuxian Chen,
Jialin Guo,
Xuchen Qi,
Donghai Wang,
Huijun Zheng,
Wei Liu,
Hong Yu,
Chunfeng Wang,
Shu Jeffrey Zhu,
Feng Guo
Affiliations
Han Li
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Jinyan Xie
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Xiuliu Guo
Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
Guilian Yang
College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China
Bin Cai
Department of Quality Management, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
Jingtianyi Liu
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Mengjia Yue
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Yixin Tang
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Gan Wang
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Shuxian Chen
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Jialin Guo
Institute of Land and Food Systems, University of British Columbia, Vancouver, BC, Canada
Xuchen Qi
Central Laboratory of Medicine, Shaoxing People’s Hospital, Shaoxing, China
Donghai Wang
Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
Huijun Zheng
Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
Wei Liu
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
Hong Yu
Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
Chunfeng Wang
College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China
Shu Jeffrey Zhu
Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China
Feng Guo
Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
Severe acute pancreatitis (SAP) is a critical illness characterized by a severe systemic inflammatory response resulting in persistent multiple organ failure and sepsis. The intestinal microbiome is increasingly appreciated to play a crucial role in modulation of AP disease outcome, but limited information is available about the identity and mechanism of action for specific commensal bacteria involved in AP-associated inflammation. Here we show that Bifidobacteria, particularly B. animalis, can protect against AP by regulating pancreatic and systemic inflammation in germ-free (GF) and oral antibiotic-treated (Abx) mouse models. Colonization by B. animalis and administration of its metabolite lactate protected Abx and GF mice from AP by reducing serum amylase concentration, ameliorating pancreatic lesions and improving survival rate after retrograde injection of sodium taurocholate. B. animalis relieved macrophage-associated local and systemic inflammation of AP in a TLR4/MyD88- and NLRP3/Caspase1-dependent manner through its metabolite lactate. Supporting our findings from the mouse study, clinical AP patients exhibited a decreased fecal abundance of Bifidobacteria that was inversely correlated with the severity of systemic inflammatory responses. These results may shed light on the heterogeneity of clinical outcomes and drive the development of more efficacious therapeutic interventions for AP, and potentially for other inflammatory disorders.
