Abstract
Altered fecal levels of chromogranins (Cg) and secretogranins (Sg) are demonstrated in irritable bowel syndrome (IBS), but their role in IBS pathophysiology remains unknown. This study aimed to determine if granins are associated with bacterial composition, immune activation and IBS symptoms. Protein levels of fecal granins (CgA, CgB, SgII and SgIII) were analysed with immunoassays. Mucosal mRNA expression of granins, TPH1 and immune markers were evaluated with RT-qPCR. 16S rRNA gene sequencing was performed on fecal and mucosal bacteria. The intestinal granin profile, based on fecal protein levels and mucosal mRNA expression, could not discriminate between IBS patients (n = 88) and healthy subjects (HS, n = 33). IBS patients dominated by high fecal or mucosal granin levels, respectively, did not differ in symptom or immune profiles. Fecal-dominated and mucosal-dominated granin clusters of IBS patients and HS, demonstrated separate fecal and mucosal bacterial profiles and high fecal abundance of granins were associated with a less diverse bacterial composition and the Bacteroides enterotype. The intestinal granin profiles of IBS patients and HS are linked to the intestinal bacterial composition, diversity and enterotypes. These findings suggest that granins may be one of several host-produced factors regulating the microbiota composition of the intestine.
Highlights
Irritable bowel syndrome (IBS) is a chronic disorder in which patients suffer from gastrointestinal symptoms such as pain/discomfort, bloating and altered bowel habits[1]
In irritable bowel syndrome (IBS) patients and healthy subjects the Bacteroides enterotype (n = 15) had higher fecal protein levels of granins (CgA, chromogranin B (CgB), secretogranin II (SgII) and SgIII) but lower bacterial alpha diversity compared to the Clostridiales (n = 59) and Prevotella enterotype (n = 8, Fig. 5b,c). This exploratory study demonstrated a low discrimination between IBS patients and healthy subjects based on the intestinal granin profile
Two distinct clusters dominated by high levels of fecal granins or high expression of mucosal granins were identified both in IBS patients and healthy subjects, and the fecal-dominated and mucosal-dominated granin clusters of IBS patients and healthy subjects demonstrated separate fecal and mucosal bacterial profiles
Summary
Irritable bowel syndrome (IBS) is a chronic disorder in which patients suffer from gastrointestinal symptoms such as pain/discomfort, bloating and altered bowel habits[1]. Previous studies have shown altered intestinal protein levels of chromogranins and secretogranins (granins) in IBS patients compared to healthy subjects[7,8,9,10]. It is currently not known whether granins are part of IBS aetiology, or linked to IBS symptoms. Chromogranins and secretogranins share physiochemical properties including their acidity, ability to bind calcium, tendency to form aggregates and their multiple cleavage sites. Together they form the granin family, which include chromogranin A (CgA), chromogranin B (CgB), secretogranin II (SgII) and secretogranin III14. The ability of granins to in vitro affect bacterial growth both directly and indirectly suggests a potential link between intestinal bacterial composition and granins
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