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Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids

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Abstract

Background/Aims

A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex.

Methods

Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured.

Results

HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation.

Conclusions

The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

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Abbreviations

HFD:

High-fat diet

C. butyricum :

Clostridium butyricum

BA:

Bile acid

TJP:

Tight function protein

MPO:

Myeloperoxidase

IL:

Interleukin

TNF:

Tumor necrosis factor

SCFA:

Short-chain fatty acid

SPF:

Specific-pathogen-free

PBS:

Phosphate-buffered saline

CFU:

Colony-forming unit

ELISA:

Enzyme-linked immunosorbent assay

RT-qPCR:

Real-time quantitative polymerase chain reaction

H&E:

Hematoxylin and eosin

CA:

Cholic acid

CDCA:

Chenodeoxycholic acid

DCA:

Deoxycholic acid

IBS:

Irritable bowel syndrome

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Funding

This work was supported by Grant No. 06-2020-0317 from the Seoul National University Bundang Hospital Research Fund. In addition, this work was supported by Ildong Pharmaceutical, Co., Ltd.

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Author notes

  1. Yonghoon Choi and Soo In Choi contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea

    Yonghoon Choi, Soo In Choi, Nayoung Kim, Ryoung Hee Nam, Jae Young Jang, Cheol Min Shin & Dong Ho Lee

  2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Nayoung Kim & Dong Ho Lee

  3. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea

    Hee Young Na

  4. Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, South Korea

    Huitae Min, Yeon-Ran Kim & Yeong-Jae Seok

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  1. Yonghoon Choi
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Contributions

Conceptualization and generator: NK. Data curation: SIC, NK. Formal analysis: YC, SIC. Funding acquisition: NK. Investigation: SIC, RHN, JYJ, NK. Methodology: SIC, RHN, JYJ, NK. Project administration: NK, Y-JS. Resources: HM, Y-RK. Supervision: NK, HYN, Y-JS. Writing—original draft: YC, SIC. Writing—review and editing: NK, CMS, DHL.

Corresponding author

Correspondence to Nayoung Kim.

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Conflict of interest

The authors have no conflicts of interest relevant to this article to disclose.

Ethical approval

This study was carried out in accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals of South Korea. The protocol was approved by the Institutional Animal Care and Use Committee of Seoul National University Bundang Hospital (Permission No. BA1506-178/027-01).

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This study is exempt from consent, since it is an animal experiment.

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Choi, Y., Choi, S.I., Kim, N. et al. Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids. Dig Dis Sci 68, 2427–2440 (2023). https://doi.org/10.1007/s10620-023-07835-2

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