Altered metabolome and microbiome features provide clues in understanding irritable bowel syndrome and depression comorbidity

Abstract

Irritable bowel syndrome (IBS) is one of the functional gastrointestinal disorders characterized by chronic and/or recurrent symptoms of abdominal pain and irregular defecation. Changed gut microbiota has been proposed to mediate IBS; however, contradictory results exist, and IBS-specific microbiota, metabolites, and their interactions remain poorly understood. To address this issue, we performed metabolomic and metagenomic profiling of stool and serum samples based on discovery (n = 330) and validation (n = 101) cohorts. Fecal metagenomic data showed moderate dysbiosis compared with other diseases, in contrast, serum metabolites showed significant differences with greater power to distinguish IBS patients from healthy controls. Specifically, 726 differentially abundant serum metabolites were identified, including a cluster of fatty acyl-CoAs enriched in IBS. We further identified 522 robust associations between differentially abundant gut bacteria and fecal metabolites, of which three species including Odoribacter splanchnicus, Escherichia coli, and Ruminococcus gnavus were strongly associated with the low abundance of dihydropteroic acid. Moreover, dysregulated tryptophan/serotonin metabolism was found to be correlated with the severity of IBS depression in both fecal and serum metabolomes, characterized by a shift in tryptophan metabolism towards kynurenine production. Collectively, our study revealed serum/fecal metabolome alterations and their relationship with gut microbiome, highlighted the massive alterations of serum metabolites, which empower to recognize IBS patients, suggested potential roles of metabolic dysregulation in IBS pathogenesis, and offered new clues to understand IBS depression comorbidity. Our study provided a valuable resource for future studies, and would facilitate potential clinical applications of IBS featured microbiota and/or metabolites.

Phenethylamine-producing gut bacteria induces diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

“…Emerging evidence reveals that gut microbiota plays an important role in the pathophysiology of IBS. In alignment with other studies, our previous findings have reported significant changes in the structure of gut microbiota in patients with IBS, especially in IBS-D (Han et al, 2021; Jeffery et al, 2020; Zhao et al, 2020). Transplantation of fecal microbiota from IBS-D patients results in IBS-like symptoms including accelerated GI transit and intestinal barrier dysfunction in recipient germ-free mice (De Palma et al, 2017).…”

“…Phenethylamine-producing bacteria analysis in IBS-D patients Metagenomics data of IBS-D patients and healthy volunteers were obtained as previously described (Han et al, 2021). Correlation analysis was conducted between serum 5-HT level and fecal PEA level with PEA-producing bacteria in IBS-D patients.…”

Repeated inflammatory dural stimulation-induced cephalic allodynia causes alteration of gut microbial composition in rats

“…Patients with IBS have a higher prevalence odd of migraine, while migraineurs with a long headache history and high headache frequency have a higher chance of being diagnosed with IBS [ 33 , 34 ]. The roles of intestinal microbiota and gut-brain axis may provide plausible explanations for migraine and its gastrointestinal comorbidities [ 5 ]. Host-microbiota interactions participate in various physiological and pathological events, including host homeostasis, energy metabolism, cognition, behavior and nociception [ 35 , 36 ].…”

“…Functional gastrointestinal disorders, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), are common comorbidities of migraine [ 3 , 4 ]. These gastrointestinal disorders, together with extraintestinal comorbid neurological diseases, are linked to gut microbial dysbiosis [ 5 ]. Previous studies have demonstrated that the gut microbiota not only plays a key role in visceral pain, but also participates in the modulation of chronic pain [ 6 , 7 ].…”

Nutraceuticals and Physical Activity as Antidepressants: The Central Role of the Gut Microbiota

“…Irritable bowel syndrome is a common gastrointestinal disorder causing abdominal pain and irregular defecation, associated with changes in gut microbiota. In order to understand IBS depression comorbidity, Han et al [ 78 ] analyzed serum/fecal metabolome alterations related to microbiota in IBS patients. A quantity of 726 differentially abundant serum metabolites, including a cluster of fatty acyl-CoAs enriched in IBS, have been identified.…”