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Upregulation of Intestinal NLRP6 Inflammasomes After Roux-en-Y Gastric Bypass Promotes Gut Immune Homeostasis

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Abstract

Objective

Roux-en-Y gastric bypass (RYGB) could affect immunological activity after surgery. We examined the role of RYGB on the NOD-like receptor pyrin domain containing-6 (NLRP6) in the intestine after surgery in rat models.

Methods

Expression of intestinal NLRP6 in the lean, obesity, RYGB, and sham-pair fed (PF) groups was analyzed by quantitative RT-PCR, Western blotting, and immunohistochemistry. Gut microbiota abundance was determined by 16S rRNA sequencing. Cohousing experiments were conducted to analyze the effects of gut microbiota. Inflammatory cell infiltration and gut permeability were further validated.

Results

Obese rats had decreased intestinal NLRP6 levels, which could be restored by RYGB but not by calorie restriction. This regulation was dependent on the gut microbiota-related metabolites, taurine, and histamine. After RYGB, there were increased levels of taurine, which could positively affect NLRP6 expression. The pair-fed groups showed increased histamine, which had the opposite effects on NLRP6. Obese rats had greater intestinal permeability along with increased CD8+ T cell infiltration. However, RYGB but not calorie restriction could restore these changes in a manner, dependent on gut NLRP6 expression.

Conclusions

In rat models, RYGB could efficiently restore abnormal gut permeability and reduce inflammation in the intestine, depending on reactivation of NLRP6.

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Funding

This study was supported by National Key Basic Research Program of China (No.2015CB5540007); National Natural Science Foundation of China (No.81472740, 81200276 and 81700488); Natural Science Foundation of Hubei Province of China (No.2014CFA060 and 2015CFB710); Research Fund of Public Welfare in Health Industry, Health and Family Plan Committee of China (No.201402015); Natural Science Foundation of Huazhong University of Science and Technology (No.5001530030), and Health and Family Planning Youth Project Foundation of Hubei Province, China (No.WJ2015Q001).

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Geng Wang, Qingbo Wang, Jie Bai, Ning Zhao, Yu Wang, Kaixiong Tao, Guobin Wang & Zefeng Xia

  2. Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Qingbo Wang

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

    Rui Zhou

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

    Wen Kong & Tianshu Zeng

Authors
  1. Geng Wang
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  2. Qingbo Wang
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  3. Jie Bai
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  4. Ning Zhao
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  5. Yu Wang
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  11. Zefeng Xia
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Corresponding author

Correspondence to Zefeng Xia.

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The authors declare that they have no conflict of interest.

A Statement of Animal Rights/Ethical Approval

All procedures in this study were approved by the Ethics Committee for Animal Research of Tongji Medicine College.

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Geng Wang and Qingbo Wang are co-first authors.

Electronic Supplementary Material

Supplementary Figure1

(SFig 1). A. Changes of body weight after surgery. B-C. Expression of NLRP6 by explants cultured with increasing doses of histamine or taurine. D. Infiltration of macrophages and CD4+T cells in the intestine in ND, HFD, RYGB and Sham-PF groups. E. Intestinal Muc gene expressions in different groups. ND: normal diet group. HFD: high fat diet group. RYGB: HFD rats after RYGB surgery. Sham-PF: HFD rats after sham surgery and received pair-fed control (PNG 1663 kb)

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Supplementary Table 1

The primer sequences of the target. (DOCX 13 kb)

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Wang, G., Wang, Q., Bai, J. et al. Upregulation of Intestinal NLRP6 Inflammasomes After Roux-en-Y Gastric Bypass Promotes Gut Immune Homeostasis. OBES SURG 30, 327–335 (2020). https://doi.org/10.1007/s11695-019-04152-4

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