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The Influence of Bifidobacterium bifidum and Bacteroides fragilis on Enteric Glial Cell–Derived Neurotrophic Factors and Inflammasome

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Abstract

Enteric glial cells (EGCs) and enteric glial–derived neurotrophic factor (GDNF) are directly involved in intestinal inflammation. In this study, we sought to examine the possible mechanisms for how Bifidobacterium bifidum (B.b.) and Bacteroides fragilis (B.f.) influence EGC regulation. In this study, lipopolysaccharide (LPS) and interferon-γ (IFN-γ) were used as exogenous stimuli of EGCs to establish an intestinal inflammation model. After stimulation with LPS and IFN-γ, B.b. and B.f. supernatants were used to activate EGCs and to examine EGC immune mechanisms. For this purpose, qRT-PCR, western blotting, and laser scanning confocal microscopy (LSCM) were used to detect the expression of NLRP3, NLRP6, NGF, NT-3, IL-18, IL-1β, and caspase-1. We found that EGCs, after stimulation with LPS and IFN-γ, could express NLRP3, NLRP6, NT-3, NGF, IL-18, IL-1β, and caspase-1 through LSCM. In intestinal inflammation, B.b. and B.f. could trigger an increase in NGF and NT-3 expression in EGCs in order to protect the intestine. Furthermore, B.b. and B.f. could upregulate NLRP3 expression in EGCs and promote an inflammatory response. B.b. had a dual regulatory role in EGC NLRP6 expression, while B.f. inhibited NLRP6 protein expression. Moreover, B.b. could decrease the expression of IL-18, IL-1β, and caspase-1 in EGCs in order to inhibit the inflammatory response. Contrary to this, B.f. could upregulate IL-18, IL-1β, and caspase-1 expression in EGCs in order to promote the inflammatory response. B.b. and B.f. can influence the expression of NGF, NT-3, NLRP3, NLRP6, IL-18, IL-1β, and caspase-1 in EGCs in order to inhibit or promote intestinal inflammation.

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Data Availability

The datasets generated and analyzed during the present study are available from the corresponding author on reasonable request.

Abbreviations

B.b.:

Bifidobacterium bifidum

B.f.:

Bacteroides fragilis

EGCs:

enteric glial cells

LPS:

lipopolysaccharide

IFN-p:

interferon-c

qRT-PCR:

quantitative real-time PCR

LSCM:

laser scanning confocal microscopy

IBS:

irritable bowel syndrome

PI-IBS:

post-infection IBS

GFAP:

glial fibrillary acidic protein

CD:

Crohnfibrillary

NLR:

NOD-like receptor

GDNF:

neurotrophic factors

NGF:

nerve growth factor

NT-3:

neurotrophin 3

SD:

Sprague-Dawley

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Funding

This work was supported by grants from the Natural Science Foundation of Hubei Province (2014CFB688) and the Natural Science Research Project of Hubei Provincial Department of Education (D20141207).

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Author notes

  1. Peng-chun Yang, Xi-jun Li and Yan-hua Yang contributed equally to this work.

Authors and Affiliations

  1. Affiliated Renhe Hospital of Three Gorges University, Yichang, 443001, China

    Peng-chun Yang, Xi-jun Li, Yan-hua Yang, Shi-yu Li, Cai-hua Yan, Jing Wang, Qin Wang & Chi-bing Dai

  2. Yichang Yiling Hospital, Yichang, 443100, China

    Xi-jun Li

  3. Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China

    Wei Qian & Xiao-hua Hou

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  1. Peng-chun Yang
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  3. Yan-hua Yang
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  4. Wei Qian
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Contributions

Pengchun Yang and Xijun Li performed most of the experiment and data analysis and wrote the manuscript. Wei Qian, Jing Wang, and Qin Wang provided experiment assistance. Shiyu Li and Caihua Yan contributed to the interpretation of the data and analyses. Xiaohua Hou and Chibing Dai performed experimental design and guidance. All of the authors have read and approved the manuscript.

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Correspondence to Chi-bing Dai.

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This study was approved by the ethics committee of Three Gorges University. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Yang, Pc., Li, Xj., Yang, Yh. et al. The Influence of Bifidobacterium bifidum and Bacteroides fragilis on Enteric Glial Cell–Derived Neurotrophic Factors and Inflammasome. Inflammation 43, 2166–2177 (2020). https://doi.org/10.1007/s10753-020-01284-z

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