Exploring the role of gut microbiota in rheumatoid arthritis: the effects of diet and drug supplementation

Abstract

Rheumatoid Arthritis (RA) is a chronic autoimmune disease that mostly breaks out at the joints. It further causes bone erosion and decreased life quality due to severe pain. Current drugs are mainly focused on reducing pain, but unable to terminate the disease progression. This study aims to determine the effect of diet types (Western, Vegan and Mediterranean) on RA progression. Some dietary supplements and drug administration (Huayu-Qiangshen-Tongbi formula or Leflunomide plus Methotrexate) in a six-month-period were also simulated to elucidate their effects on gut microbiota growth and exchange metabolite fluxes. The computational analyses showed that Haemophilus parainfluenzae had the highest growth rate in the RA community with the Western diet. Enterococcus faecalis was the most notable bacterial species considering butyrate exchange rates without any dependency on the diet; however diet type became important for Clostridium celatum for acetate and formate exchanges. Focal interactions for RA communities signify Mediterranean diet had the most homogeneous exchange flux distribution. With iron and ornithine supplementation, Clostridium celatum outshined the rest of the bacteria in the RA community with the potential being an RA biomarker. The Mediterranean diet could be studied further for drug administration studies since the bacterial species under this diet exhibited different outputs. In the near future, by utilizing the potential of the gut microbiota to be altered with diet, it might be possible to manipulate the progression of RA.

Keywords: Amino acids; Diet; Elasticity; Gut microbiota; Metabolite fluxes; Rheumatoid arthritis; SCFA.

Fig. 1

Growth rate comparison of communities (HC vs. RA) according to the diet type. HC-healthy control community; RA- rheumatoid arthritis community

Fig. 2

Chord diagram for the bacteria knockouts for all three diet types and two communities. To be clear in this figure, it is subdivided into six parts: a) Western-HC, b) Western-RA, c) MD - HC, d) MD - RA, e) Vegan - HC, f) Vegan- RA

Fig. 2

Chord diagram for the bacteria knockouts for all three diet types and two communities. To be clear in this figure, it is subdivided into six parts: a) Western-HC, b) Western-RA, c) MD - HC, d) MD - RA, e) Vegan - HC, f) Vegan- RA

Fig. 2

Chord diagram for the bacteria knockouts for all three diet types and two communities. To be clear in this figure, it is subdivided into six parts: a) Western-HC, b) Western-RA, c) MD - HC, d) MD - RA, e) Vegan - HC, f) Vegan- RA

Fig. 3

SCFA (Acetate, butyrate, formate, propionate) exchange fluxes of HC and RA for MD, Vegan and Western diets. To be clear in this figure, it is subdivided into six parts: a) Western-HC, b) Western-RA, c) MD - HC, d) MD - RA, e) Vegan - HC, f) Vegan- RA

Fig. 3

SCFA (Acetate, butyrate, formate, propionate) exchange fluxes of HC and RA for MD, Vegan and Western diets. To be clear in this figure, it is subdivided into six parts: a) Western-HC, b) Western-RA, c) MD - HC, d) MD - RA, e) Vegan - HC, f) Vegan- RA

Fig. 3

SCFA (Acetate, butyrate, formate, propionate) exchange fluxes of HC and RA for MD, Vegan and Western diets. To be clear in this figure, it is subdivided into six parts: a) Western-HC, b) Western-RA, c) MD - HC, d) MD - RA, e) Vegan - HC, f) Vegan- RA

Fig. 4

Bacterial growth rate comparison for all diets before and after the iron, and ornithine supplementation. To be clear in this figure, its is subdivided into six parts; a) Western-doubled iron, b) MD-doubled iron, c) Vegan-doubled iron, d) Western- doubled ornithine, e) MD-doubled ornithine, f) Vegan-doubled ornithine

Fig. 4

Bacterial growth rate comparison for all diets before and after the iron, and ornithine supplementation. To be clear in this figure, its is subdivided into six parts; a) Western-doubled iron, b) MD-doubled iron, c) Vegan-doubled iron, d) Western- doubled ornithine, e) MD-doubled ornithine, f) Vegan-doubled ornithine

Fig. 4

Bacterial growth rate comparison for all diets before and after the iron, and ornithine supplementation. To be clear in this figure, its is subdivided into six parts; a) Western-doubled iron, b) MD-doubled iron, c) Vegan-doubled iron, d) Western- doubled ornithine, e) MD-doubled ornithine, f) Vegan-doubled ornithine

Fig. 5

SCFA exchange comparison for all diets before and after the iron, and ornithine supplementation. To be clear in this figure, it is subdivided into six parts: a) Western-doubled iron, b) MD-doubled iron, c) Vegan doubled iron, d) Western- doubled ornithine, e) MD-doubled ornithine, f) Vegan-doubled ornithine

Fig. 5

SCFA exchange comparison for all diets before and after the iron, and ornithine supplementation. To be clear in this figure, it is subdivided into six parts: a) Western-doubled iron, b) MD-doubled iron, c) Vegan doubled iron, d) Western- doubled ornithine, e) MD-doubled ornithine, f) Vegan-doubled ornithine

Fig. 5

SCFA exchange comparison for all diets before and after the iron, and ornithine supplementation. To be clear in this figure, it is subdivided into six parts: a) Western-doubled iron, b) MD-doubled iron, c) Vegan doubled iron, d) Western- doubled ornithine, e) MD-doubled ornithine, f) Vegan-doubled ornithine

Fig. 6

SCFA exchange flux values for HTQ-treated RA patients across three diets (Western, MD, Vegan) at four time points (m0, m1, m3, m6)

Fig. 7

SCFA exchange flux values for LEF-treated RA patients across three diets (Western, MD, Vegan) at four time points (m0, m1, m3, m6)