The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases

doi:10.3390/biomedicines12081760

Review

. 2024 Aug 5;12(8):1760.

doi: 10.3390/biomedicines12081760.

The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases

Affiliations

¹ Department of Experimental and Clinical Medicine, Division of Rheumatology, Scleroderma Unit, AOU Careggi, University of Florence, 50139 Florence, Italy.
² Department of Experimental and Clinical Medicine, Division of Internal Medicine AOUC, University of Florence, 50134 Florence, Italy.
³ Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy.
⁴ Raynaud's and Scleroderma Programme, NIHR Biomedical Research Centre, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS9 7JT, UK.
⁵ Department of Rheumatology, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁶ Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, 20132 Milan, Italy.

PMID: 39200224
PMCID: PMC11351188
DOI: 10.3390/biomedicines12081760

Review

The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases

Carmela Coccia et al. Biomedicines. 2024.

. 2024 Aug 5;12(8):1760.

doi: 10.3390/biomedicines12081760.

Affiliations

¹ Department of Experimental and Clinical Medicine, Division of Rheumatology, Scleroderma Unit, AOU Careggi, University of Florence, 50139 Florence, Italy.
² Department of Experimental and Clinical Medicine, Division of Internal Medicine AOUC, University of Florence, 50134 Florence, Italy.
³ Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy.
⁴ Raynaud's and Scleroderma Programme, NIHR Biomedical Research Centre, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS9 7JT, UK.
⁵ Department of Rheumatology, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁶ Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, 20132 Milan, Italy.

PMID: 39200224
PMCID: PMC11351188
DOI: 10.3390/biomedicines12081760

Abstract

The gut microbiota is a complex ecosystem of microorganisms residing in the human gastrointestinal tract, playing a crucial role in various biological processes and overall health maintenance. Dysbiosis, an imbalance in the composition and function of the gut microbiota, is linked to systemic autoimmune diseases (SAD). Short-chain fatty acids (SCFAs), especially butyrate, produced by the gut microbiota through the fermentation of dietary fibers, play a significant role in immunomodulation and maintaining intestinal homeostasis. Butyrate is essential for colonocyte energy, anti-inflammatory responses, and maintaining intestinal barrier integrity. Studies show reduced butyrate-producing bacteria in SAD patients, suggesting that increasing butyrate levels could have therapeutic benefits. Butyrate's anti-inflammatory effects and its potential therapeutic role have been studied in rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, systemic sclerosis, and Behçet's disease. Despite promising in vitro and animal model results, human studies are limited, and the optimal strategies for modulating dysbiosis in SADs remain elusive. This review explores the current evidence on the immunoregulatory role of butyrate and its potential therapeutic effects in SAD.

Keywords: Behçet’s disease; Sjogren’s syndrome; butyrate; microbiota; rheumatoid arthritis; short-chain fatty acids; systemic autoimmune diseases; systemic lupus erythematosus; systemic sclerosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Mechanism of action of butyrate and its role in modulating the immune system. HDAC: histone deacetylase, SMA: smooth muscle actin.

See this image and copyright information in PMC

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References

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1. Rasouli-Saravani A., Jahankhani K., Moradi S., Gorgani M., Shafaghat Z., Mirsanei Z., Mehmandar A., Mirzaei R. Role of microbiota short-chain fatty acids in the pathogenesis of autoimmune diseases. Biomed. Pharmacother. 2023;162:114620. doi: 10.1016/j.biopha.2023.114620. - DOI - PubMed

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[1] Wang Y., Wei J., Zhang W., Doherty M., Zhang Y., Xie H., Li W., Wang N., Lei G., Zeng C. Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies. EBioMedicine. 2022;80:104055. doi: 10.1016/j.ebiom.2022.104055. - DOI - PMC - PubMed

[2] Wang Y., Wei J., Zhang W., Doherty M., Zhang Y., Xie H., Li W., Wang N., Lei G., Zeng C. Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies. EBioMedicine. 2022;80:104055. doi: 10.1016/j.ebiom.2022.104055. - DOI - PMC - PubMed

[3] Chang P.V., Hao L., Offermanns S., Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA. 2014;111:2247–2252. doi: 10.1073/pnas.1322269111. - DOI - PMC - PubMed

[4] Chang P.V., Hao L., Offermanns S., Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA. 2014;111:2247–2252. doi: 10.1073/pnas.1322269111. - DOI - PMC - PubMed

[5] Furusawa Y., Obata Y., Fukuda S., Endo T.A., Nakato G., Takahashi D., Nakanishi Y., Uetake C., Kato K., Kato T., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–450. doi: 10.1038/nature12721. - DOI - PubMed

[6] Furusawa Y., Obata Y., Fukuda S., Endo T.A., Nakato G., Takahashi D., Nakanishi Y., Uetake C., Kato K., Kato T., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–450. doi: 10.1038/nature12721. - DOI - PubMed

[7] Teng F., Klinger C.N., Felix K.M., Bradley C.P., Wu E., Tran N.L., Umesaki Y., Wu H.-J.J. Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer’s Patch T Follicular Helper Cells. Immunity. 2016;44:875–888. doi: 10.1016/j.immuni.2016.03.013. - DOI - PMC - PubMed

[8] Teng F., Klinger C.N., Felix K.M., Bradley C.P., Wu E., Tran N.L., Umesaki Y., Wu H.-J.J. Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer’s Patch T Follicular Helper Cells. Immunity. 2016;44:875–888. doi: 10.1016/j.immuni.2016.03.013. - DOI - PMC - PubMed

[9] Rasouli-Saravani A., Jahankhani K., Moradi S., Gorgani M., Shafaghat Z., Mirsanei Z., Mehmandar A., Mirzaei R. Role of microbiota short-chain fatty acids in the pathogenesis of autoimmune diseases. Biomed. Pharmacother. 2023;162:114620. doi: 10.1016/j.biopha.2023.114620. - DOI - PubMed

[10] Rasouli-Saravani A., Jahankhani K., Moradi S., Gorgani M., Shafaghat Z., Mirsanei Z., Mehmandar A., Mirzaei R. Role of microbiota short-chain fatty acids in the pathogenesis of autoimmune diseases. Biomed. Pharmacother. 2023;162:114620. doi: 10.1016/j.biopha.2023.114620. - DOI - PubMed

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The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases

Affiliations

The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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References

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Abstract

Conflict of interest statement

Figures

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References

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