The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.

• MeSH
• Inflammatory Bowel Diseases metabolism   pathology   MeSH
• Humans MeSH
• Monocytes metabolism   drug effects   MeSH
• Cell Movement drug effects   MeSH
• Serotonin * pharmacology   metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Intestinal Mucosa * metabolism   drug effects   pathology   immunology   MeSH
• Tumor Necrosis Factor-alpha * MeSH
• Inflammation * metabolism   pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Serotonin * MeSH
• Tumor Necrosis Factor-alpha * MeSH

One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.

• MeSH
• Acute Disease MeSH
• CD11b Antigen biosynthesis   genetics   MeSH
• Administration, Rectal MeSH
• Bacterial Translocation MeSH
• Butyrates metabolism   MeSH
• Clostridium tyrobutyricum physiology   MeSH
• Phosphoproteins biosynthesis   genetics   MeSH
• Immunocompetence MeSH
• Interleukin-18 biosynthesis   genetics   MeSH
• Colon metabolism   microbiology   pathology   MeSH
• Fatty Acids metabolism   MeSH
• Membrane Proteins biosynthesis   genetics   MeSH
• Mucin-2 biosynthesis   genetics   MeSH
• Mucins biosynthesis   MeSH
• Mice, Inbred BALB C MeSH
• Mice, SCID MeSH
• Mice MeSH
• Specific Pathogen-Free Organisms MeSH
• Probiotics therapeutic use   MeSH
• Zonula Occludens-1 Protein MeSH
• Dextran Sulfate toxicity   MeSH
• Severe Combined Immunodeficiency genetics   immunology   MeSH
• Tumor Necrosis Factor-alpha biosynthesis   genetics   MeSH
• Colitis, Ulcerative chemically induced   genetics   immunology   microbiology   pathology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CD11b Antigen MeSH
• Butyrates MeSH
• Phosphoproteins MeSH
• Interleukin-18 MeSH
• Fatty Acids MeSH
• Membrane Proteins MeSH
• Muc2 protein, mouse MeSH Browser
• Mucin-2 MeSH
• Mucins MeSH
• Zonula Occludens-1 Protein MeSH
• Dextran Sulfate MeSH
• Tjp1 protein, mouse MeSH Browser
• Tumor Necrosis Factor-alpha MeSH

Interleukin-6 (IL-6) plays an important role in regulation of intestinal inflammatory processes in inflammatory bowel disease (IBD). The levels of IL-6 in media from cultured biopsy samples were determined by ELISA in 14 Crohn's disease (CD) patients, 17 patients with ulcerative colitis (UC), and 24 healthy controls in terminal ileum, cecum, and rectum. Results were confirmed by measuring mRNA expression in selected patients. In CD patients, there were increased levels of IL-6 (expressed in picograms per milligram of biopsy tissue mass) in terminal ileum compared with controls (median, 617 vs. 90.4; p < 0.001). High IL-6 levels were found in the rectum of CD patients with active disease but normal endoscopic findings (791 vs. 131; p < 0.05). This result was confirmed by mRNA expression. There was a substantial increase of IL-6 levels in cultured cecal (median, 327 vs. 94.0; p < 0.001) and rectal mucosa (median, 282 vs.131; p < 0.05) but not in ileal mucosa of UC patients. In conclusion, IL-6 production was higher in IBD patients than in controls; it correlated with disease activity and varied among different intestinal segments. In clinically active CD patients without rectal involvement, high IL-6 levels in cultured rectal mucosa suggest immune stimulation even in the absence of macroscopic inflammation.

• MeSH
• Crohn Disease immunology   metabolism   pathology   MeSH
• Adult MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Interleukin-6 biosynthesis   immunology   MeSH
• Cells, Cultured MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger biosynthesis   MeSH
• Polymerase Chain Reaction MeSH
• Intestinal Mucosa immunology   metabolism   pathology   MeSH
• Colitis, Ulcerative immunology   metabolism   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• IL6 protein, human MeSH Browser
• Interleukin-6 MeSH
• RNA, Messenger MeSH