Beneficial effects of a probiotic blend on gastrointestinal side effects induced by leflunomide and amlodipine in a rat model

Abstract

Patients with metabolic disorders frequently suffer from side effects induced by long-term oral medications. The present study using a rat model system indicated that leflunomide (LF) and amlodipine (AMD), the active ingredients contained in the medications for rheumatoid arthritis and hypertension, respectively, appeared to induce various bowel problems including constipation and inflammation. In the small and large intestine, LF increased the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 compared to the null control and AMD increased the expression of both TNF-α and IL-1β, although its effect on IL-6 was only increased in the large intestine. It is noteworthy that the probiotic blend tested was found to alleviate intestinal complications caused by LF and AMD. Analysis of the gut microbiota revealed that AMD induced compositional changes in the gut microbiota. Namely, members of the phylum Bacteroidetes, which constituted only about 0.3% of the microbiota in the null control, made up more than 10% of the total composition in the AMD-administered rats. Interestingly, the probiotic blend was also found to normaliSe the gut microbiota.

Relationship Between the Gastrointestinal Side Effects of an Anti-Hypertensive Medication and Changes in the Serum Lipid Metabolome

“…As shown in Figure 1, the control group and the AMD group were clearly divided into two clusters on the PCA score plot, whereas the AMD+PB group displayed a pattern almost identical to that of the control group. This result is in good agreement with the previous finding that the PB alleviated intestinal complications caused by AMD [19].…”

“…The probiotic blend used in this study was previously shown to have beneficial effects on human subjects with irritable bowel syndrome [45] and on animals with indomethacin-induced small intestine injury [46]. In our previous experiment, it was found to bring down increased levels of inflammatory cytokines in AMD-administered rats [19]. Glucocorticoids, including corticosterone in rodents and cortisol in humans, are anti-inflammatory steroid hormones [47,48].…”

“…We previously reported that amlodipine (AMD), the active ingredient in a hypertension medicine, is an aggravating factor in various bowel problems, including constipation and inflammation. This is because it induces compositional changes in the gut microbiota, since normalization of the gut microbiota alleviates intestinal complications caused by AMD [19]. To investigate the effects of the gut microbiome on the host, we performed a comparative analysis of lipid metabolome in serum samples from rats that received saline (null control), AMD, or AMD plus a probiotic blend (AMD+PB).…”

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

“…This could be explained because in this previous study, a great part of HT patients had taken antihypertensive drugs and they were in a more advance hypertension grade. It has been recently reported that the hypertensive drug treatment can induce compositional changes in the gut microbiota and also inflammation 24 , so drug-induced gut microbiome shifts could have strongly influenced in their results. Moreover, in contrast to our study, in which we assessed diet composition and other lifestyle outcomes such as physical activity and sleep habits showing no significant differences among both groups, they did not control any environmental factor that could also affect the gut microbial community.…”

Role of the gut microbiome in cardiovascular drug response: The potential for clinical application

“…78 Song et al reported improvements in GI side effects of amlodipine therapy with probiotics. 79 Amlodipine, as well as bacterial dysbiosis, has been associated with diarrhea.…”