Neuroprotective role of <i>Faecalibacterium prausnitzii-derived</i> butyrate in diabetic gastrointestinal autonomic neuropathy

Lin Guo; Jie Li; Jiaming An; Jiahe Miao; Yang Yi; Keying Zhu; Qing Cai; Sijing Wang; Zhan Su; Xiaolong Ye; Yayun Wang; Minglin Pan; Qingmiao Lu; Bota Cui; Faming Zhang; Jianhua Mao; Xingyin Liu; Yibing Lu; Dafa Ding

doi:10.1016/j.jgg.2026.06.005

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Neuroprotective role of Faecalibacterium prausnitzii-derived butyrate in diabetic gastrointestinal autonomic neuropathy

doi: 10.1016/j.jgg.2026.06.005

a. Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China;
b. Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu 211166, China;
c. Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China;
d. School of Medicine, Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China;
e. Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA

Funds:

The authors acknowledge resources and support from The Experimental Center of The Second Affiliated Hospital of Nanjing Medical University. This research was funded by scientific research projects of Jiangsu Provincial Health and Health Commission (ZDB2020034, M2021056). Schematic representations in the graphical abstract were created using Generic Diagramming Platform (GDP). We acknowledge GDP for their assistance.

Received Date: 2025-12-18
Accepted Date: 2026-06-05
Rev Recd Date: 2026-06-03

Available Online: 2026-06-12

Abstract

Abstract

Diabetic gastrointestinal autonomic neuropathy (DGAN) is a common yet poorly understood complication of diabetes that is characterized by gastrointestinal dysmotility and enteric neurodegeneration. Here, we investigate whether gut microbiota dysbiosis contributes to DGAN pathogenesis and explore the potential involvement of microbiota-derived metabolites in enteric nervous system (ENS) injury. Gut microbiota profiling reveals disease-associated compositional alterations in patients with DGAN, including depletion of Faecalibacterium-associated signals, with Faecalibacterium prausnitzii identified as a putative species-level annotation and negatively associated with gastrointestinal symptom severity. Fecal microbiota transplantation from patients with DGAN into db/db mice aggravates gut dysmotility and increases apoptosis of ChAT⁺ and nNOS⁺ myenteric neurons. Further experiments indicate that butyrate, the predominant metabolite produced by F. prausnitzii, attenuates neuronal apoptosis under high-glucose conditions. This biological process is accompanied by enhanced BCL2 expression, downregulation of cleaved caspase-3, and activation of the PI3K/Akt signaling cascade. Collectively, our findings support the presence of a gut microbiota-ENS axis in DGAN and identify butyrate as an important candidate neuroprotective metabolite associated with F. prausnitzii. These results provide a rationale for microbiota-targeted therapeutic strategies for diabetic enteric neuropathy.
- Diabetic gastrointestinal autonomic neuropathy,
- Faecalibacterium prausnitzii,
- Butyrate,
- Enteric nervous system,
- Gut microbiome

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