Gut Microbiota–Host Interactions in Inborn Errors of Immunity

Abstract

Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.

Distribution of intraepithelial lymphocytes, mast cells, and goblet cells in the intestine of alpaca

“…It is well known that goblet cells in the intestine mainly secrete mucins, which, as an important part of the intestinal mucus layer and intestinal epithelial cells, can not only lubricate and protect the intestinal mucosal epithelium Ren et al, 2019), but are also involved in intercellular signalling transduction and the regulation of intestinal mucosa‐associated immune factors (Castagnoli et al, 2021), which can be divided into the secreted mucins and the membrane‐bound mucins according to their existing forms (Etzold & Juge, 2014). It has been shown that bacterial products and their inflammatory factors can induce the formation of sulphonyltransferase, thus making MUC2 sulphate (Ren et al, 2019).…”

Inborn errors of immunity and related microbiome

“…There are two pathways of IgA production by gut plasma cells—T-cell-dependent and T-cell-independent—which require cooperation with epithelial cells, DCs, and innate lymphoid cells (ILCs) ( 10 ). The first pathway typically occurs in Peyer’s patches and microbiota-specific, whereas the second pathway mostly takes place in the lamina propria and isolated lymphoid follicles, leading to the exclusion of microorganisms from the gut ( 52 ). Additionally, the microbiota induces IgA2 class switching through a CD4+ T-cell-independent pathway by linking B cells in lamina propria to intestinal epithelial cells via a TLR-inducible and APRIL-requiring signaling program ( 53 ).…”

Inborn Errors of Immunity in the Premature Infant: Challenges in Recognition and Diagnosis

“…The digestive tract is frequently affected in the setting of IEI through a variety of mechanisms (58). Clinical presentations of feeding intolerance, bloody stools, diarrhea, and failure to thrive can manifest in the premature neonate and overlap with signs that may be seen in IEI.…”