The effects of orally administered Bacillus coagulans and inulin on prevention and progression of rheumatoid arthritis in rats

Abstract

Background: Probiotics have been considered as an approach to addressing the consequences of different inflammatory disorders. The spore-forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic inulin also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota.

Objective: In the present study, an in vivo model was conducted to investigate the possible influences of probiotic B. coagulans and prebiotic inulin, both in combination and/or separately, on the downregulation of immune responses and the progression of rheumatoid arthritis (RA), using arthritis-induced rat model.

Design: Forty-eight healthy male Wistar rats were randomly categorized into six experimental groups as follows: 1) control: normal healthy rats fed with standard diet, 2) disease control (RA): arthritis-induced rats fed with standard diet, 3) prebiotic (PRE): RA+ 5% w/w long-chain inulin, 4) probiotic (PRO): RA+ 10(9) spores/day B. coagulans by orogastric gavage, 5) synbiotic (SYN): RA+ 5% w/w long-chain inulin and 10(9) spores/day B. coagulans, and 6) treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with the listed diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund's adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by the biochemical parameters and paw thickness. Biochemical assay for fibrinogen (Fn), serum amyloid A (SAA), and TNF-α and alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28, and 35 (7, 14 and 21 days post RA induction), respectively.

Results: Pretreatment with PRE, PRO, and SYN diets significantly inhibits SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, was seen in the PRE, PRO, and SYN groups (P < 0.001), which was similar to the anti-inflammatory effect of indomethacin. Furthermore, no significant anti-inflammatory effects were observed following different treatments using α1 AGp as an RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001).

Conclusion: The results of this study indicate that the oral intake of probiotic B. coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat.

Keywords: Bacillus coagulans; animal model; inulin; rheumatoid arthritis.

Fig. 1

The schematic overview of the experimental study.

Fig. 2

Effect of oral administration of Bacillus coagulans and inulin on plasma fibrinogen levels in complete Freund's adjuvant (CFA) induced male Wistar rats. For details of the treatment groups, see Table 1. Values are expressed as mean for eight animals. Bars represent standard deviation values. The different letters in the same sampling day indicate significant differences (P<0.05).

Fig. 3

Effect of oral administration of Bacillus coagulans and inulin on plasma serum amyloid A (SAA) levels in CFA-induced male Wistar rats. For details of the treatment groups, see Table 1. Values are expressed as mean for eight animals. Bars represent standard deviation values. The different letters in the same sampling day indicate significant differences (P<0.05).

Fig. 4

Effect of oral administration of Bacillus coagulans and inulin on TNF-α levels in CFA-induced male Wistar rats. For details of the treatment groups, see Table 1. Values are expressed as mean for eight animals. Bars represent standard deviation values. The different letters in the same sampling day indicate significant differences (P<0.05).

Fig. 5

Effect of oral administration of Bacillus coagulans and inulin on alpha-1-acid glycoprotein (α₁AGp) levels in CFA-induced male Wistar rats. For details of the treatment groups, see Table 1. Values are expressed as mean for eight animals. Bars represent standard deviation values. The different letters in the same sampling day indicate significant differences (P<0.05).

Fig. 6

Effect of oral administration of Bacillus coagulans and inulin on paw diameter in CFA-induced male Wistar rats. For details of the treatment groups, see Table 1. Values are expressed as mean for eight animals. Bars represent standard deviation values.