Folic acid attenuates chronic visceral pain by reducing clostridiales abundance and hydrogen sulfide production

Abstract

Background: Irritable bowel syndrome (IBS) related chronic visceral pain affects 20% of people worldwide. The treatment options are very limited. Although the scholarly reviews have appraised the potential effects of the intestinal microbiota on intestinal motility and sensation, the exact mechanism of intestinal microbiota in IBS-like chronic visceral pain remains largely unclear. The purpose of this study is to investigate whether Folic Acid (FA) attenuated visceral pain and its possible mechanisms. Methods: Chronic visceral hyperalgesia was induced in rats by neonatal colonic inflammation (NCI). 16S rDNA analysis of fecal samples from human subjects and rats was performed. Patch clamp recording was used to determine synaptic transmission of colonic-related spinal dorsal horn. Results: Alpha diversity of intestinal flora was increased in patients with IBS, as well as the obviously increased abundance of Clostridiales order (a main bacteria producing hydrogen sulfide). The hydrogen sulfide content was positive correlation with visceral pain score in patients with IBS. Consistently, NCI increased Clostridiales frequency and hydrogen sulfide content in feces of adult rats. Notably, the concentration of FA was markedly decreased in peripheral blood of IBS patients compared with non-IBS human subjects. FA supplement alleviated chronic visceral pain and normalized the Clostridiales frequency in NCI rats. In addition, FA supplement significantly reduced the frequency of sEPSCs of neurons in the spinal dorsal horn of NCI rats. Conclusion: Folic Acid treatment attenuated chronic visceral pain of NCI rats through reducing hydrogen sulfide production from Clostridiales in intestine.

Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice

“…Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder characterized by chronic visceral pain, typically presenting as abdominal discomfort or pain along with altered bowel habits. 1 – 3 Globally, IBS affects approximately 11 % of the population, 4 – 6 with direct economic costs exceeding $ 1 billion in the United States. 7 , 8 The pathogenesis of IBS centers around abnormalities in visceral sensation, neurologic processing of pain, gut-brain interactions, and psychosocial distress.…”

Paraventricular thalamus‐insular cortex circuit mediates colorectal visceral pain induced by neonatal colonic inflammation in mice

“…The incidence of IBS has been increasing in recent years, 4 whereas the etiology of IBS is not completely understood, which prevents effective treatments and thus makes a negative impact on the physiological and psychological well‐being of affected individuals 5,6 and increases the burden of the health care system. Currently, most research on chronic colorectal visceral pain focuses on the peripheral aspects, with limited research addressing the contribution of the central nervous system 7–11 . Therefore, exploring the regulatory mechanisms of the central nervous system on IBS colorectal visceral pain may promote understanding of IBS pathogenesis and identifying new therapeutic targets.…”

“…Currently, most research on chronic colorectal visceral pain focuses on the peripheral aspects, with limited research addressing the contribution of the central nervous system. 7 , 8 , 9 , 10 , 11 Therefore, exploring the regulatory mechanisms of the central nervous system on IBS colorectal visceral pain may promote understanding of IBS pathogenesis and identifying new therapeutic targets.…”