Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis

Häupl T, Sörensen T, Smiljanovic B, Darcy M, Scheder-Bieschin J, Steckhan N, Hartmann AM, Koppold DA, Stuhlmüller B, Skriner K, Walewska BM, Hoppe B, Bonin M, Burmester GR, Schendel P, Feist E, Liere K, Meixner M, Kessler C, Grützkau A, Michalsen A · Journal of Clinical Medicine · 2023 June 28

DOI 10.3390/jcm12134359

Objective

To investigate the impact of reducing the intestinal microbiome through bowel cleansing and fasting on disease activity and immune markers in rheumatoid arthritis (RA) patients.

Conclusions

Disease activity scores improved in 19 of 20 RA patients after the intervention, with some achieving remission, along with decreased levels of inflammatory markers, suggesting a potential link between the gut microbiota and RA-specific inflammation.

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Insights

Rheumatoid arthritis-specific inflammation can be linked directly to the intestinal microbiota, thus, nutritional interventions against gut dysbiosis could function as a causal therapeutic approach.

The study initiated by reducing the intestinal microbiome in 20 Rheumatoid Arthritis patients through bowel cleansing and a week of fasting, limiting the intake to 250 kcal/day. It also employed immune monitoring and sequencing of the microbiome. A control group constituting patients with metabolic syndrome was incorporated to serve as a non-inflammatory baseline. To understand the fluctuation and impact on disease activity, disease activity scores were calculated and cytometric profiling was performed, tracing up to 46 different surface markers. Additionally, serum levels of certain cytokines and indicators of mucosal barrier disruption were monitored. The change in intestinal microbiota, i.e., the effect of fasting on arthritogenic bacteria and the shift in microbial composition, was analyzed using sequencing. The detection of more eukaryotic, predominantly fungal colonizers in RA patients was also observed to understand their potential involvement. Finally, the study investigated the observed increase in endogenous cortisol levels during fasting.