Higher serum levels of short-chain fatty acids are associated with non-progression to arthritis in individuals at increased risk of RA

Martinsson, Κjell; Dürholz, Kerstin; Schett, Georg; Zaiss, Mario M.; Kastbom, Alf

doi:10.1136/annrheumdis-2021-221386

Cited by 25 publications

(19 citation statements)

References 6 publications

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“…Although numerous studies have reported that metabolites of gut microbiota are associated with the progression of arthritis and suggest butyrate as a therapeutic strategy for arthritis, these studies have not specifically explored the relationship between gut microbiota produced-derived metabolites and drug therapy ( Kim et al, 2018 ; Rosser et al, 2020 ; He et al, 2022 ; Martinsson et al, 2022 ). Based on the correlation between intestinal microbiota and drug toxicity, this study evaluated the influence of gut microbiota on drug efficacy, which is helpful to solve the problems of intestinal toxicity and unsatisfactory response of MTX.…”

Section: Discussionmentioning

confidence: 99%

Bacteroides fragilis participates in the therapeutic effect of methotrexate on arthritis through metabolite regulation

Zhou

Dong²,

Zhao³

et al. 2022

Front. Microbiol.

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Methotrexate (MTX) is a preferred disease-modifying anti-rheumatic drug in the management of rheumatoid arthritis (RA). However, the toxicity and inefficiency of MTX limit its clinical application. Gut microbiota has been implicated in the side effects and efficacy of MTX. In this study, the analysis of the gut microbiota in RA patients revealed that the abundances of intestinal Bacteroides fragilis was reduced after MTX treatment. We observed that MTX has no obvious therapeutic effect in the absence of B. fragilis, while transplantation of B. fragilis restored the efficacy of MTX in antibiotics-pretreated collagen-induced arthritis (CIA) mice. In addition, B. fragilis gavage was accompanied by an increase in butyrate. Supplementation of butyrate restored the response to MTX in gut microbiota-deficient mice, to a similar level achieved by B. fragilis gavage. These results show that gut microbiota-regulated butyrate plays an essential role in the efficacy of MTX, which will provide new strategies to improve the effectiveness of methotrexate in RA treatment.

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Section: Discussionmentioning

confidence: 99%

Bacteroides fragilis participates in the therapeutic effect of methotrexate on arthritis through metabolite regulation

Zhou

Dong²,

Zhao³

et al. 2022

Front. Microbiol.

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“…A recent study assessing levels of SCFAs in blood and stool of patients has shown reduced levels of SCFAs in patients with RA compared to controls, although diverging effects were detected for serum and stool concentrations and per study [ 62 , 63 ]. Others have suggested that high levels of SCFAs may provide a protective effect in individuals at risk for RA development [ 61 , 75 ]. Animal studies have also suggested a beneficial role of higher SCFA concentrations: Takahashi et al (2021), using a collagen-induced arthritis (CIA) and an SKG (i.e., T-cell mediated) mouse model for RA, showed that in vitro, butyrate increased follicular T regulatory cells, which reduce secretion of cytokines necessary for B cell activation and class switching.…”

Section: Scfa Interventions In Inflammatory Disordersmentioning

confidence: 99%

Regulation of CD4+ and CD8+ T Cell Biology by Short-Chain Fatty Acids and Its Relevance for Autoimmune Pathology

Schiweck

Thanrajah

Aichholzer

et al. 2022

IJMS

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The gut microbiota encodes a broad range of enzymes capable of synthetizing various metabolites, some of which are still uncharacterized. One well-known class of microbiota-derived metabolites are the short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate and valerate. SCFAs have long been considered a mere waste product of bacterial metabolism. Novel results have challenged this long-held dogma, revealing a central role for microbe-derived SCFAs in gut microbiota-host interaction. SCFAs are bacterial signaling molecules that act directly on host T lymphocytes by reprogramming their metabolic activity and epigenetic status. They have an essential biological role in promoting differentiation of (intestinal) regulatory T cells and in production of the anti-inflammatory cytokine interleukin-10 (IL-10). These small molecules can also reach the circulation and modulate immune cell function in remote tissues. In experimental models of autoimmune and inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis or diabetes, a strong therapeutic potential of SCFAs through the modulation of effector T cell function was observed. In this review, we discuss current research activities toward understanding a relevance of microbial SCFA for treating autoimmune and inflammatory pathologies from in vitro to human studies.

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“…Recently, short-chain fatty acids (SCFAs) have been shown to influence the development and progression of RA [ 24 , 25 , 26 ]. SCFAs (e.g., butyrate, acetate, and propionate) are the main metabolic products of anaerobic bacterial fiber fermentation in the intestine and have many effects on host physiology such as acting as an energy source for colonocytes, regulating the gut barrier, and influencing inflammatory response and immunity [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…A high-fiber diet increases SCFA levels and decreases the inflammatory response in patients with RA [ 28 ]. Furthermore, an increased intake of dietary fiber significantly improved the physical function and quality of life in RA patients [ 24 , 25 , 28 ]. It appears likely that a healthy, high-fiber diet may be a game-changer for patients with a high risk of developing RA.…”

Section: Introductionmentioning

confidence: 99%

Nutrition Patterns and Their Gender Differences among Rheumatoid Arthritis Patients: A Descriptive Study

et al. 2022

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Dietary factors probably play a role in the pathogenesis and clinical course of rheumatoid arthritis (RA). There is a paucity of specific dietary guidelines for RA patients and little information on their implementation in daily life. Therefore, this study aimed to determine the nutritional status and provision of nutritional education among outpatients with RA. Here, 61 patients were included with a sex ratio of 2.03 (f/m). Based on BMI, 22% of women were overweight and 32% obese, whereas 50% of men were overweight and 30% obese. Fasting blood and a 3-day estimated dietary record were collected. Additionally, patients were asked whether they had already received information about a specific diet as part of their disease treatment plan. Elevated total cholesterol levels were found in 76% of women and in 60% of men caused by increased non-HDL-C levels. The dietary intake assessment showed a lower self-reported intake of energy, polyunsaturated fat, carbohydrates, fiber, and several micronutrients than recommended. Regarding healthy eating, all patients reported familiarity with dietary recommendations, but found it difficult to implement the recommendations into their diets. These findings suggested that RA patients need more specific recommendations and education in clinical practice to improve the quality of their diet.

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Higher serum levels of short-chain fatty acids are associated with non-progression to arthritis in individuals at increased risk of RA

Cited by 25 publications

References 6 publications

Bacteroides fragilis participates in the therapeutic effect of methotrexate on arthritis through metabolite regulation

Bacteroides fragilis participates in the therapeutic effect of methotrexate on arthritis through metabolite regulation

Regulation of CD4+ and CD8+ T Cell Biology by Short-Chain Fatty Acids and Its Relevance for Autoimmune Pathology

Nutrition Patterns and Their Gender Differences among Rheumatoid Arthritis Patients: A Descriptive Study

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