Sounding the alarm in the lung with TL1A.

Environmental airborne antigens are central to the development of allergic asthma, but the cellular processes that trigger disease remain incompletely understood. In this report, Schmitt et al. (https://doi.

The gut microbiome regulates the clinical efficacy of sulfasalazine therapy for IBD-associated spondyloarthritis.

Sulfasalazine is a prodrug known to be effective for the treatment of inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA), but the mechanistic role for the gut microbiome in regulating its clinical efficacy is not well understood. Here, treatment of 22 IBD-pSpA subjects with sulfasalazine identifies clinical responders with a gut microbiome enriched in Faecalibacterium prausnitzii and the capacity for butyrate production. Sulfapyridine promotes butyrate production and transcription of the butyrate synthesis gene but in F.

Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15.

Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3 regulatory T (Treg) cells and local immune homeostasis.

Agr2-associated ER stress promotes adherent-invasive E. coli dysbiosis and triggers CD103 dendritic cell IL-23-dependent ileocolitis.

Endoplasmic reticulum (ER) stress is associated with Crohn's disease (CD), but its impact on host-microbe interaction in disease pathogenesis is not well defined. Functional deficiency in the protein disulfide isomerase anterior gradient 2 (AGR2) has been linked with CD and leads to epithelial cell ER stress and ileocolitis in mice and humans. Here, we show that ileal expression of AGR2 correlates with mucosal Enterobactericeae abundance in human inflammatory bowel disease (IBD) and that Agr2 deletion leads to ER-stress-dependent expansion of mucosal-associated adherent-invasive Escherichia coli (AIEC), which drives Th17 cell ileocolitis in mice.

Increased Primary Bile Acids with Ileocolonic Resection Impact Ileal Inflammation and Gut Microbiota in Inflammatory Bowel Disease.

Background: Most Crohn's disease [CD] patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impacts of ileocolectomy-induced bile acid [BA] perturbations on intestinal microbiota and inflammation are unknown.

Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease.

Background: Patients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.

Aim: To determine proportions and factors associated with vitamin C deficiency in CD and UC patients.

Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer.

Inflammatory bowel disease (IBD) is a chronic life-long inflammatory disease affecting almost 2 million Americans. Although new biologic therapies have been developed, the standard medical treatment fails to selectively control the dysregulated immune pathways involved in chronic colonic inflammation. Further, IBD patients with uncontrolled colonic inflammation are at a higher risk for developing colorectal cancer (CRC).

Human gut bacteria produce Τ17-modulating bile acid metabolites.

The microbiota modulates gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17A (T17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits T17 cell differentiation.

Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome.

Hundreds of microbiota genes are associated with host biology/disease. Unraveling the causal contribution of a microbiota gene to host biology remains difficult because many are encoded by nonmodel gut commensals and not genetically targetable. A general approach to identify their gene transfer methodology and build their gene manipulation tools would enable mechanistic dissections of their impact on host physiology.

Impact of Inflammatory Bowel Disease Therapies on Durability of Humoral Response to SARS-CoV-2 Vaccination.

Immunization against the spike protein of SARS-CoV-2 reduces transmission and severe outcomes. However, little is known regarding the impact of immune-mediated diseases and immunosuppressive medications on the efficacy of vaccination. Vaccination immunity is transient, with breakthrough cases increasing at longer time intervals since the last dose.

Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease.

Secretory immunoglobulin A (sIgA) plays an important role in gut barrier protection by shaping the resident microbiota community, restricting the growth of bacterial pathogens and enhancing host protective immunity via immunological exclusion. Here, we found that a portion of the microbiota-driven sIgA response is induced by and directed towards intestinal fungi. Analysis of the human gut mycobiota bound by sIgA revealed a preference for hyphae, a fungal morphotype associated with virulence.

Transferable Immunoglobulin A-Coated Odoribacter splanchnicus in Responders to Fecal Microbiota Transplantation for Ulcerative Colitis Limits Colonic Inflammation.

Background & Aims: Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC.

Methods: Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC.

Thymic development of gut-microbiota-specific T cells.

Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described.

Decoding the matrix: multiomics reveals host-microbe biomarker for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine associated with genetic susceptibility and alterations in the intestinal microbiome. Multiomics data developed and analyzed over the last several decades have yielded an unprecedented amount of genetic and microbial data. But how do we pinpoint mechanistic insight into the host-microbe relationship that will ultimately enable better care for patients with IBD? In this issue of the JCI, Grasberger et al.

Adherent-invasive E. coli metabolism of propanediol in Crohn's disease regulates phagocytes to drive intestinal inflammation.

Adherent-invasive E. coli (AIEC) are enriched in the intestinal microbiota of patients with Crohn's disease (CD) and promote intestinal inflammation. Yet, how AIEC metabolism of nutrients impacts intestinal homeostasis is poorly defined.

A Diamond in the Rough: IgA-Seq Signatures Stratify New Onset IBD.

Intestinal immunoglobulin (Ig)A binds to distinct commensals and pathobionts, but do these IgA-coated bacterial communities define clinical characteristics of inflammatory disease? In this issue of Cell Host & Microbe, Shapiro et al. comprehensively analyze IgA-coated bacteria in new onset inflammatory bowel disease (IBD), revealing their potential in guiding precision therapy and diagnostic stratification.

Patient-Preferences Favoring Treatment Discontinuation Are Reduced With Vedolizumab and Ustekinumab Compared With TNF Antagonists in Inflammatory Bowel Disease.

Background: Nonadherence to biologic therapy in inflammatory bowel disease (IBD) is associated with risk of relapse, immunogenicity, and disease complications. Significant nonadherence prevalence is reported with tumor necrosis factor (TNF) antagonists but the risk of nonadherence with newer biologics with better safety profiles is unknown. This study aimed to investigate if IBD patient-preferences favoring biologic discontinuation vary by biologic class and analyze factors associated with such preferences.