Increased Ileal Immunoglobulin A Production and Immunoglobulin A-Coated Bacteria in Diarrhea-Predominant Irritable Bowel Syndrome, 2020, Liu et a

Dolphin · Apr 11, 2020

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Increased Ileal Immunoglobulin A Production and Immunoglobulin A-Coated Bacteria in Diarrhea-Predominant Irritable Bowel Syndrome

Liu, Yi MD1,2; Yuan, Xunyi MD3; Li, Lixiang PhD1,4; Lin, Lin MD1; Zuo, Xiuli MD, PhD1; Cong, Yingzi PhD5,6; Li, Yanqing MD, PhD1,4

Author Information
Clinical and Translational Gastroenterology: March 2020 - Volume 11 - Issue 3 - p e00146
doi: 10.14309/ctg.0000000000000146
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Abstract

OBJECTIVES:
Immune activation and intestinal microbial dysbiosis could induce diarrhea-predominant irritable bowel syndrome (IBS-D). We examined the roles of ileal immunoglobulin A (IgA) and IgA-coated bacteria in IBS-D pathogenesis.

METHODS:
Peripheral blood, fecal samples, and ileal and cecal biopsies were collected from 32 healthy volunteers and 44 patients with IBS-D. Quantitative reverse transcriptase polymerase chain reaction was used to assess differential gene expression. IgA levels in the blood and fecal samples were quantified by an enzyme-linked immunosorbent assay. IgA+ cells were assessed by immunofluorescence imaging. Flow-cytometry-based IgA+ bacterial cell sorting and 16S rRNA gene sequencing (IgA-SEQ) was used to isolate and identify fecal IgA+ bacteria.

RESULTS:
Fecal IgA, particularly IgA1, was upregulated in patients with IBS-D. IgA class switch and B cell–activating factor-receptor were increased in the terminal ileum of patients. The intestinal microbiota composition was altered in patients compared with that in controls. IgA-SEQ showed that the proportion of fecal IgA-coated bacteria was increased significantly in patients with IBS-D. IgA+ bacteria in patients with IBS-D showed higher abundances of Escherichia–Shigella, Granulicatella, and Haemophilus compared with healthy controls and IgA− bacteria in patients with IBS-D. The Escherichia–Shigella IgA coating index was positively correlated with anxiety and depression. The Escherichia–Shigella relative abundance, luminal IgA activity, and some altered IgA-coated bacteria were positively associated with the clinical manifestations of IBS-D.

DISCUSSION:
Microbial dysbiosis may promote the terminal ileal mucosa to produce higher levels of IgA, increasing the proportion of IgA-coated bacteria by activating IgA class switching, which might regulate local inflammation and clinical manifestations in IBS-D. IgA may mediate the effects of microbial dysbiosis on the pathogenesis of IBS-D.
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Dolphin · Apr 11, 2020

Study Highlights

WHAT IS KNOWN

✓ Low-grade inflammation occurs in the intestinal mucosa of patients with IBS, and increased humoral immunity occurs in diarrhea-predominant IBS.

✓ Fecal IgA is involved in regulating intestinal homeostasis and the pathogenesis of IBD.

✓ How humoral responses to microbiota regulate the pathogenesis of IBS-D and the roles of mucosal IgA and IgA-coated bacteria in the pathogenesis of IBS-D are unclear.

WHAT IS NEW HERE

✓ Patients with IBS-D exhibited activated IgA class switching and higher IgA levels in the terminal ileum.

✓ Patients with IBS-D presented an increased proportion of IgA-coated bacteria, which was related to the strength of the inflammatory response triggered by intestinal bacteria.

✓ Ileal IgA and IgA-coated bacteria were associated with the major clinical manifestations of IBS-D.

✓ Escherichia–Shigella, particularly IgA-coated Escherichia–Shigella, which was anomalously enriched and positively correlated with anxiety and depression scores, was associated with the clinical manifestations of IBS-D.

TRANSLATIONAL IMPACT

✓ Our study revealed that patients with IBS-D exhibit higher levels of IgA and IgA class switching and an increased proportion of IgA-coated bacteria, which are associated with the clinical manifestations. IgA may mediate the effects of microbial dysbiosis on the pathophysiology of IBS-D. Understanding the role of IgA in the pathogenesis of IBS-D will provide a foundation for potential therapeutic interventions to prevent or ameliorate inflammatory reactions of IBS-D.

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