Secretory IgA: controlling the gut microbiota

2021 ◽  
Author(s):  
Oliver Pabst ◽  
Ana Izcue
Keyword(s):  
Gut Microbiota ◽  
Secretory Iga

scholarly journals IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jason R. Catanzaro ◽  
Juliet D. Strauss ◽  
Agata Bielecka ◽  
Anthony F. Porto ◽  
Francis M. Lobo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
16S Rrna Gene Sequencing ◽  
Iga Deficiency ◽  
Secretory Iga ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Microbiota Composition ◽  
Antibody Isotype ◽  
Selective Iga Deficiency ◽  
Gut Microbiota Composition

Abstract Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that mucosal secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and taxa-specific antibody coating of the gut microbiota in 15 sIgAd subjects and matched controls. Despite the secretion of compensatory IgM into the gut lumen, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls. These alterations were characterized by a trend towards decreased overall microbial diversity as well as significant shifts in the relative abundances of specific microbial taxa. While secretory IgA in healthy controls targeted a defined subset of the microbiota via high-level coating, compensatory IgM in sIgAd subjects showed less specificity than IgA and bound a broader subset of the microbiota. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community.

scholarly journals Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis

2021 ◽  
Vol 8 (4) ◽  
pp. e997
Author(s):  
Delphine Sterlin ◽  
Martin Larsen ◽  
Jehane Fadlallah ◽  
Christophe Parizot ◽  
Marina Vignes ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Flow Cytometry ◽  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Secretory Iga ◽  
Autologous Serum ◽  
Immune Homeostasis ◽  
Bacterial Strains ◽  
Serum Igg ◽  
Rrna Sequencing

ObjectiveBased on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS.MethodsWe investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing.ResultsWe show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (r = −0.647, p < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, p < 0.001).ConclusionsGut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.

scholarly journals Secretory IgA in Intestinal Mucosal Secretions as an Adaptive Barrier against Microbial Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9254
Author(s):  
Bernadeta Pietrzak ◽  
Katarzyna Tomela ◽  
Agnieszka Olejnik-Schmidt ◽  
Andrzej Mackiewicz ◽  
Marcin Schmidt
Keyword(s):  
Gut Microbiota ◽  
Plasma Cells ◽  
Intestinal Barrier ◽  
Secretory Iga ◽  
Microbiota Composition ◽  
Lymphoid Follicles ◽  
Lymphoid Structures ◽  
Antibody Class ◽  
Mucosal Secretions ◽  
Gut Microbiota Composition

Secretory IgA (SIgA) is the dominant antibody class in mucosal secretions. The majority of plasma cells producing IgA are located within mucosal membranes lining the intestines. SIgA protects against the adhesion of pathogens and their penetration into the intestinal barrier. Moreover, SIgA regulates gut microbiota composition and provides intestinal homeostasis. In this review, we present mechanisms of SIgA generation: T cell-dependent and -independent; in different non-organized and organized lymphoid structures in intestinal lamina propria (i.e., Peyer’s patches and isolated lymphoid follicles). We also summarize recent advances in understanding of SIgA functions in intestinal mucosal secretions with focus on its role in regulating gut microbiota composition and generation of tolerogenic responses toward its members.

scholarly journals Dietary protein increases T cell independent sIgA production through changes in gut microbiota-derived extracellular vesicles

2020 ◽  
Author(s):  
Jian Tan ◽  
Duan Ni ◽  
Jemma Taitz ◽  
Gabriela Veronica Pinget ◽  
Mark Read ◽  
...  
Keyword(s):  
T Cell ◽  
Gut Microbiota ◽  
Extracellular Vesicles ◽  
Dietary Protein ◽  
Causal Link ◽  
High Protein ◽  
Secretory Iga ◽  
High Concentrations ◽  
Isocaloric Diets ◽  
Fat Diets

AbstractSecretory IgA (sIgA) is a key mucosal component ensuring host-microbiota mutualism. Using nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, we identified dietary protein as the major driver of sIgA production. Protein-driven sIgA induction was not mediated by T cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high-protein fed mice produced significantly higher quantities of extracellular vesicles (EV), compared to those of mice fed high-carbohydrate or high-fat diets. These EV activated TLR4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We showed that succinate, produced in high concentrations by microbiota of high-protein fed animals, increased the generation of reactive oxygen species by bacteria, which in turn promoted EV production. This is the first report establishing a causal link between dietary macronutrient composition, gut microbial EV release and host sIgA response.

scholarly journals A fermented formula in pre-term infants: clinical tolerance, gut microbiota, down-regulation of faecal calprotectin and up-regulation of faecal secretory IgA

2011 ◽  
Vol 105 (12) ◽  
pp. 1843-1851 ◽  
Author(s):  
Florence Campeotto ◽  
Antonia Suau ◽  
Nathalie Kapel ◽  
Fabien Magne ◽  
Vivian Viallon ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gastrointestinal Disease ◽  
Streptococcus Thermophilus ◽  
Abdominal Distension ◽  
Secretory Iga ◽  
Bacterial Colonisation ◽  
Term Infants ◽  
Faecal Calprotectin ◽  
Increased Risk ◽  
Culture Independent

Intestinal bacterial colonisation in pre-term infants is delayed compared with full-term infants, leading to an increased risk of gastrointestinal disease. Modulation of colonisation through dietary supplementation with probiotics or prebiotics could decrease such a risk. The present study evaluated clinical tolerance, the effects on gut microbiota, and inflammatory and immunological mucosal responses to an infant formula adapted for pre-term infants that included in its manufacturing process a fermentation step with two probiotic strains, Bifidobacterium breve C50 and Streptococcus thermophilus 065, inactivated by heat at the end of the process. A total of fifty-eight infants (gestational age: 30–35 weeks), fed either the fermented pre-term formula or a standard pre-term formula, were followed up during their hospital stay. Clinical tolerance, faecal microbiota using a culture and a culture-independent method (temporal temperature gel electrophoresis), faecal calprotectin and secretory IgA were analysed weekly. No difference was observed regarding anthropometric data and digestive tolerance, except for abdominal distension, the incidence of which was lower in infants fed the fermented formula for 2 weeks. Bacterial colonisation was not modified by the type of feeding, particularly for bifidobacteria. Faecal calprotectin was significantly lower in infants fed the fermented formula for 2 weeks, and secretory IgA increased with both mother's milk and the fermented formula. The fermented formula was well tolerated and did not significantly modulate the bacterial colonisation but had benefits on inflammatory and immune markers, which might be related to some features of gastrointestinal tolerance.

scholarly journals Differences in immune status and fecal SCFA between Indonesian stunted children and children with normal nutritional status

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254300
Author(s):  
Ingrid S. Surono ◽  
Fasli Jalal ◽  
Syukrini Bahri ◽  
Andreas Romulo ◽  
Pratiwi Dyah Kusumo ◽  
...  
Keyword(s):  
Nutritional Status ◽  
Gut Microbiota ◽  
Immune Status ◽  
Specific Pattern ◽  
Secretory Iga ◽  
Macronutrient Intake ◽  
Microbiota Composition ◽  
Normal Children ◽  
Branched Chain ◽  
The Individual

We recently showed that the gut microbiota composition of stunted children was different from that of children with normal nutritional status. Here, we compared immune status and fecal microbial metabolite concentrations between stunted and normal children, and we correlated macronutrient intake (including energy), metabolites and immune status to microbiota composition. The results show that macronutrient intake was lower in stunted children for all components, but after correction for multiple comparison significant only for energy and fat. Only TGF-β was significantly different between stunted children and children of normal nutritional status after correction for multiple comparisons. TNF-alpha, IL-10, lipopolysaccharide binding protein in serum and secretory IgA in feces were not significantly different. Strikingly, all the individual short-chain and branched-chain fatty acids were higher in fecal samples of stunted children (significant for acetate, valerate and total SCFA). These metabolites correlated with a number of different microbial taxa, but due to extensive cross-feeding between microbes, did not show a specific pattern. However, the energy-loss due to higher excretion in stunted children of these metabolites, which can be used as substrate for the host, is striking. Several microbial taxa also correlated to the intake of macronutrients (including dietary fibre) and energy. Eisenbergiella positively correlated with all macronutrients, while an uncharacterized genus within the Succinivibrionaceae family negatively correlated with all macronutrients. These, and the other correlations observed, may provide indication on how to modulate the gut microbiota of stunted children such that their growth lag can be corrected. Trail registered at https://clinicaltrials.gov/ct2/show/NCT04698759.

scholarly journals IgA-deficient humans exhibit gut microbiota dysbiosis despite production of compensatory IgM

2018 ◽  
Author(s):  
Jason R Catanzaro ◽  
Juliet D Strauss ◽  
Agata Bielecka ◽  
Anthony F Porto ◽  
Francis M Lobo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
16S Rrna Gene Sequencing ◽  
Iga Deficiency ◽  
Secretory Iga ◽  
Intestinal Lumen ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Antibody Isotype ◽  
Selective Iga Deficiency ◽  
Gut Microbiota Composition

ABSTRACTImmunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) is the most common primary immunodeficiency in humans and is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and IgA or IgM coating of the gut microbiota in 15 sIgAd subjects and 15 matched controls. Although sIgAd subjects secreted a significant amount of IgM into the intestinal lumen, this was insufficient to fully compensate for the lack of secretory IgA. Indeed, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls, which was characterized by a trend towards decreased overall microbial diversity and significant shifts in the relative abundances of specific microbial taxa. While IgA targets a defined subset of the microbiota via high-level coating, compensatory IgM binds a broader subset of the microbiota in a less targeted manner. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community that promotes human health, enhances resistance to infection, and is resilient to perturbation.

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