Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease

Shajib, Sharif; Chauhan, Usha; Adeeb, Salman; Chetty, Yeshale; Armstrong, David; Halder, Smita; Marshall, John K.; Khan, Waliul I.

doi:10.1093/jcag/gwy039

Cited by 36 publications

(45 citation statements)

References 37 publications

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“…Released 5-HT further activates intestinal serotonergic receptors, which causes alterations in gut functions. 35 Furthermore, IBD patients suffering from diarrhea were also reported to be associated with higher levels of mucosal 5-HT, which results in visceral hypersensitivity and altered gastrointestinal motility. 35 Therefore, these evidences suggest that 5-HT is crucial in the pathogenesis of IBD.…”

Section: Discussionmentioning

confidence: 99%

“…35 Furthermore, IBD patients suffering from diarrhea were also reported to be associated with higher levels of mucosal 5-HT, which results in visceral hypersensitivity and altered gastrointestinal motility. 35 Therefore, these evidences suggest that 5-HT is crucial in the pathogenesis of IBD. 34,35 In the present investigation, TNBS-induced colitis rats exhibited enhanced cytokine secretions with an increased serotonin secretion in the inflamed colon which may be resulted from the perturbation of the mast cells.…”

Section: Discussionmentioning

confidence: 99%

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Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice

et al. 2019

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Background: Inflammatory bowel disease is a chronic immunoinflammatory disease of the gastrointestinal tract. Piperine, an alkaloid, has been reported to possess antioxidant, anti-inflammatory, antiapoptotic, and antiulcer potential. Aim: To elucidate the plausible mechanisms of action of piperine on experimental trinitrobenzenesufonic acid (TNBS)-induced colitis by assessing various biochemical, molecular, histological, and ultrastructural modifications. Methods: Colitis was induced in male Sprague–Dawley rats via intrarectal instillation of TNBS. Then, the rats were treated with piperine (10, 20, and 40 mg/kg, p.o.) for 14 days. Results: TNBS induced significant ( p < 0.05) colonic damage, which was assessed by disease activity index, macroscopic score, and stool consistency. The administration of piperine (20 and 40 mg/kg) significantly inhibited ( p < 0.05) these damages. Treatments with piperine (20 and 40 mg/kg) notably inhibited ( p < 0.05) the TNBS-induced elevation of oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), 5-hydroxytryptamine, and hydroxyproline content in the colon. Furthermore, colonic inducible nitric oxide synthase (iNOs), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma, and cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expressions were upregulated after TNBS instillation and piperine (20 and 40 mg/kg) significantly attenuated ( p < 0.05) these elevated mRNA expressions. TNBS decreased the expressions of tight junction (TJ) protein (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and increased the expressions of proapoptotic (caspase-1) protein. These expressions were markedly inhibited ( p < 0.05) by piperine treatment. Histological and ultrastructural studies of transmission electron microscopy suggested that piperine significantly ameliorated ( p < 0.05) TNBS-induced colonic aberrations. Conclusion: Piperine ameliorated the progression of TNBS-induced colitis by modulating the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha/nuclear factor-kappa B signaling pathway, thus inhibiting the overexpression of proinflammatory cytokines (TNF-α and IL’s), COX-2, iNOs, oxido-nitrosative stress, and proapoptotic proteins (caspase-1) that may improve the expression of TJ protein (claudin-1, occludin, and ZO-1).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice

et al. 2019

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“…5-HT is considered as an important signaling molecule in maintaining GI homeostasis. Changes in EC cell numbers and 5-HT have been observed in a number of GI diseases including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) as well as in animal models of various enteric infections, including with the helminth parasite, Trichuris muris (8)(9)(10)(11)(12)(13)(14). Recently, we reported the reduced severity of colitis and downregulated production of proinflammatory cytokines in Tph1deficient (Tph1 2/2 ) mice, which have significantly reduced 5-HT in the gut compared with wild-type (WT) mice after dextran sulfate sodium (DSS)-and 2,4-dinitrobenzenesulfonic acid-induced colitis (15).…”

mentioning

confidence: 99%

TLR2 Plays a Pivotal Role in Mediating Mucosal Serotonin Production in the Gut

Wang

Kwon

Dewan

et al. 2019

The Journal of Immunology

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Serotonin (5-hydroxytryptamine [5-HT]) is a key enteric signaling molecule that mediates various physiological processes in the gut. Enterochromaffin (EC) cells in the mucosal layer of the gut are the main source of 5-HT in the body and are situated in close proximity to the gut microbiota. In this study, we identify a pivotal role of TLR2 in 5-HT production in the gut. Antibiotic treatment reduces EC cell numbers and 5-HT levels in naive C57BL/6 mice, which is associated with downregulation of TLR2 expression but not TLR1 or TLR4. TLR2-deficient (Tlr2 2/2) and Myd88 2/2 mice express lower EC cell numbers and 5-HT levels, whereas treatment with TLR2/1 agonist upregulates 5-HT production in irradiated C57BL/6 mice, which are reconstituted with Tlr2 2/2 bone marrow cells, and in germ-free mice. Human EC cell line (BON-1 cells) release higher 5-HT upon TLR2/1 agonist via NF-kB pathway. Tlr2 2/2 mice and anti-TLR2 Ab-treated mice infected with enteric parasite, Trichuris muris, exhibited attenuated 5-HT production, compared with infected wild-type mice. Moreover, excretory-secretory products from T. muris induce higher 5-HT production in BON-1 cells via TLR2 in a dose-dependent manner, whereby the effect of excretory-secretory products is abrogated by TLR2 antagonist. These findings not only suggest an important role of TLR2 in mucosal 5-HT production in the gut by resident microbiota as well as by a nematode parasite but also provide, to our knowledge, novel information on the potential benefits of targeting TLR2 in various gut disorders that exhibit aberrant 5-HT signaling.

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“…Elevated FOLH1 expression has been reported in intestinal biopsies of patients with IBD and inhibiting FOLH1 activity ameliorates IBD associated abnormalities in mouse models [35,36]. HTR3A encodes one of the serotonin receptors and increased HTR3A colonic expression has been observed in patients with Crohn's disease [37]. UCP2 encodes for mitochondrial Uncoupling Protein 2 and has been implicated in several autoimmune diseases [38].…”

Section: Microbial Gene Family Analysis Reveals Three Psoriasis Subgrmentioning

confidence: 99%

Metagenomic Analysis of the Gut Microbiome in Psoriasis Reveals Three Subgroups with Distinct Host-Microbe Interactions

Chang

Yan

Singh

et al. 2020

Preprint

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Background Psoriasis is a chronic, inflammatory skin disease that impacts 2–3% of the global population. Besides skin manifestations, psoriasis patients have increased susceptibility to a number of comorbidities including psoriatic arthritis, cardiovascular disease, and inflammatory bowel disease. To understand the systemic component of psoriasis pathogenesis, we examined the fecal metagenome, host colonic transcriptome, and host peripheral blood immune profiles of psoriasis patients and healthy controls. Results Our analysis showed increased functional diversity in the gut microbiome of psoriasis patients. In addition, we identified microbial species that preferentially associate with psoriasis patients and which have been previously found to associate with other autoimmune diseases. Intriguingly, our data reveal new insights about psoriasis disease heterogeneity, as we identified three psoriasis subgroups that have distinct microbial and host features. Finally, integrating microbial and host features revealed host-microbe interactions that are specific to psoriasis or particular psoriasis subgroups. Conclusion To our knowledge, this is the first study that provides a comprehensive view of gut microbial function and corresponding host response in psoriasis patients. Our findings provide insight into factors that may affect the development of comorbidities in psoriasis patients and may hold diagnostic potential for early identification of psoriasis patients at risk for these comorbidities.

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Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease

Cited by 36 publications

References 37 publications

Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice

Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice

TLR2 Plays a Pivotal Role in Mediating Mucosal Serotonin Production in the Gut

Metagenomic Analysis of the Gut Microbiome in Psoriasis Reveals Three Subgroups with Distinct Host-Microbe Interactions

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