scholarly journals IgA deficiency destabilizes immunological homeostasis towards intestinal microbiota and increases the risk of systemic immune dysregulation

2021 ◽  
Author(s):  
Peyton E Conrey ◽  
Lidiya Denu ◽  
Kaitlin C. O'Boyle ◽  
Jamal Green ◽  
Jeffrey Maslanka ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Intestinal Barrier ◽  
16S Rrna Gene Sequencing ◽  
Immune Dysregulation ◽  
Iga Deficiency ◽  
Fecal Microbiota ◽  
Intestinal Microbiome ◽  
Secretory Iga ◽  
Rrna Gene

Mammals produce large quantities of mucosal and systemic antibodies that maintain the intestinal barrier, shape the intestinal microbiome and promote lifelong mutualism with commensal microbes. Here, we developed an integrated host-commensal approach combining microbial flow cytometry and 16s rRNA gene sequencing to define the core microbes that induce mucosal and systemic antibodies in pediatric selective Immunoglobulin A (IgA) deficient and household control siblings with CyTOF analysis to determine the impacts of IgA deficiency on host cellular immune phenotype. In healthy controls, mucosal secretory IgA and IgM antibodies coat an overlapping subset of microbes, predominantly Firmicutes and Proteobacteria. Serum IgG antibodies target a similar consortium of fecal microbes, revealing connections between mucosal and systemic antibody networks. Unexpectedly, IgM provides limited compensation for IgA in children lacking intestinal IgA. Furthermore, we find broad systemic immune dysregulation in a subset of children and mice lacking IgA, including enhanced IgG targeting of fecal microbiota, elevated levels of inflammatory and allergic cytokines and alterations in T cell activation state. Thus, IgA tunes systemic interactions between the host and commensal microbiota. Understanding how IgA tunes baseline immune tone has implications for predicting and preventing autoimmune, inflammatory and allergic diseases broadly, as well as providing improved prognostic guidance to patients with IgA deficiency.

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 Nuciferine modulates the gut microbiota and prevents obesity in high-fat diet-fed rats

2020 ◽  
Vol 52 (12) ◽  
pp. 1959-1975
Author(s):  
Yu Wang ◽  
Weifan Yao ◽  
Bo Li ◽  
Shiyun Qian ◽  
Binbin Wei ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
16S Rrna Gene Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Low Grade ◽  
Rrna Gene Sequencing

AbstractGut microbiota dysbiosis has a significant role in the pathogenesis of metabolic diseases, including obesity. Nuciferine (NUC) is a main bioactive component in the lotus leaf that has been used as food in China since ancient times. Here, we examined whether the anti-obesity effects of NUC are related to modulations in the gut microbiota. Using an obese rat model fed a HFD for 8 weeks, we show that NUC supplementation of HFD rats prevents weight gain, reduces fat accumulation, and ameliorates lipid metabolic disorders. Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that NUC changed the diversity and composition of the gut microbiota in HFD-fed rats. In particular, NUC decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio and bacteria involved in lipid metabolism, whereas it increased the relative abundance of SCFA-producing bacteria in HFD-fed rats. Predicted functional analysis of microbial communities showed that NUC modified genes involved in LPS biosynthesis and lipid metabolism. In addition, serum metabolomics analysis revealed that NUC effectively improved HFD-induced disorders of endogenous metabolism, especially lipid metabolism. Notably, NUC promoted SCFA production and enhanced intestinal integrity, leading to lower blood endotoxemia to reduce inflammation in HFD-fed rats. Together, the anti-obesity effects of NUC may be related to modulations in the composition and potential function of gut microbiota, improvement in intestinal barrier integrity and prevention of chronic low-grade inflammation. This research may provide support for the application of NUC in the prevention and treatment of obesity.

scholarly journals Oral Vaccination against Lawsoniaintracellularis Changes the Intestinal Microbiome in Weaned Piglets

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2082
Author(s):  
Robin B. Guevarra ◽  
Jae Hyoung Cho ◽  
Jin Ho Cho ◽  
Jun Hyung Lee ◽  
Hyeri Kim ◽  
...  
Keyword(s):  
Block Design ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Fecal Microbiota ◽  
Negative Control ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Significant Shift ◽  
Diversity Analysis ◽  
Treatment Groups

Lawsoniaintracellularis, which causes porcine proliferative enteropathy (PPE), is a common swine intestinal pathogen that is prevalent in pig production sites worldwide. In this study, the alteration in the microbiome composition of weaned pigs was investigated in response to vaccination against L. intracellularis, using 16S rRNA gene sequencing. A total of 64 crossbred (Duroc × [Landrace × Yorkshire]) healthy weanling pigs weaned at 4 weeks of age were randomly assigned to four treatment groups (four pigs/pen; four pens/treatment), using a randomized complete block design for the 42-day trial. Pigs in the treatment groups were orally administered with three different doses (1 dose = 2 mL) of vaccine against L. intracellularis (Enterisol® Ileitis, Boehringer Ingelheim Vetmedica GmbH), namely the following: LAW1 (0.5 dose), LAW2 (1 dose), LAW3 (2 dose). A non-vaccinated group served as a negative control (CONT). Alpha diversity analysis revealed that vaccination led to significant changes in species evenness but not species richness of the gut microbiota. Beta diversity analysis revealed that vaccination against L. intracellularis caused a significant shift in the microbial community structure. At the genus level, there was a significant increase in Streptococcus and a significant decrease in Clostridium in the fecal microbiota of vaccinated pigs, regardless of dose.

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.

scholarly journals Links between fecal microbiota and the response to vaccination against influenza A virus in pigs

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Marion Borey ◽  
Fany Blanc ◽  
Gaëtan Lemonnier ◽  
Jean-Jacques Leplat ◽  
Deborah Jardet ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Influenza A ◽  
16S Rrna Gene Sequencing ◽  
Serum Levels ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Vaccine Response ◽  
Specific Igg ◽  
Rrna Gene Sequencing

AbstractThis study describes the associations between fecal microbiota and vaccine response variability in pigs, using 98 piglets vaccinated against the influenza A virus at 28 days of age (D28) with a booster at D49. Immune response to the vaccine is measured at D49, D56, D63, and D146 by serum levels of IAV-specific IgG and assays of hemagglutination inhibition (HAI). Analysis of the pre-vaccination microbiota characterized by 16S rRNA gene sequencing of fecal DNA reveals a higher vaccine response in piglets with a richer microbiota, and shows that 23 operational taxonomic units (OTUs) are differentially abundant between high and low IAV-specific IgG producers at D63. A stronger immune response is linked with OTUs assigned to the genus Prevotella and family Muribaculaceae, and a weaker response is linked with OTUs assigned to the genera Helicobacter and Escherichia-Shigella. A set of 81 OTUs accurately predicts IAV-specific IgG and HAI titer levels at all time points, highlighting early and late associations between pre-vaccination fecal microbiota composition and immune response to the vaccine.

scholarly journals Abrupt Temporal Fluctuations in the Chicken Fecal Microbiota Are Explained by Its Gastrointestinal Origin

2012 ◽  
Vol 78 (8) ◽  
pp. 2941-2948 ◽  
Author(s):  
M. Sekelja ◽  
I. Rud ◽  
S. H. Knutsen ◽  
V. Denstadli ◽  
B. Westereng ◽  
...  
Keyword(s):  
Barrier Function ◽  
16S Rrna Gene Sequencing ◽  
Fecal Microbiota ◽  
Pathogen Transmission ◽  
Rrna Gene ◽  
Multivariate Statistical ◽  
Content Type ◽  
Factors Affecting ◽  
Temporal Fluctuations ◽  
Gastric Barrier

ABSTRACTOne of the main challenges in understanding the composition of fecal microbiota is that it can consist of microbial mixtures originating from different gastrointestinal (GI) segments. Here, we addressed this challenge for broiler chicken feces using a direct 16S rRNA gene-sequencing approach combined with multivariate statistical analyses. Broiler feces were chosen because of easy sampling and the importance for pathogen transmission to the human food chain. Feces were sampled daily for 16 days from chickens with and without a feed structure-induced stimulation of the gastric barrier function. Overall, we found four dominant microbial phylogroups in the feces. Two of the phylogroups were related to clostridia, one to lactobacilli, and one toEscherichia/Shigella. The relative composition of these phylogroups showed apparent stochastic temporal fluctuations in feces. Analyses of dissected chickens at the end of the experiment, however, showed that the two clostridial phylogroups were correlated to the microbiota in the cecum/colon and the small intestine, while the upper gut (crop and gizzard) microbiota was correlated to the lactobacillus phylogroup. In addition, chickens with a stimulated gizzard also showed less of the proximate GI dominating bacterial group in the feces, supporting the importance of the gastric barrier function. In conclusion, our results suggest that GI origin is a main determinant for the chicken fecal microbiota composition. This knowledge will be important for future understanding of factors affecting shedding of both harmful and beneficial gastrointestinal bacteria through feces.

scholarly journals Alterations of gut microbiota in gestational diabetes patients during the second trimester of pregnancy in the Shanghai Han population

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yao Su ◽  
Hong-Kun Wang ◽  
Xu-Pei Gan ◽  
Li Chen ◽  
Yan-Nan Cao ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Sugar Metabolism ◽  
16S Rrna Gene Sequencing ◽  
Amino Sugar ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Second Trimester ◽  
Metabolic Hormone

Abstract Background The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. Methods Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. Results Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. Conclusion Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.

scholarly journals Translational and clinical advances in acute graft-versus-host disease

Haematologica ◽  
2020 ◽  
Vol 105 (11) ◽  
pp. 2550-2560
Author(s):  
Mahasweta Gooptu ◽  
John Koreth
Keyword(s):  
T Lymphocytes ◽  
T Cell Activation ◽  
Graft Versus Host Disease ◽  
Cell Activation ◽  
Therapeutic Strategies ◽  
Intestinal Microbiome ◽  
Host Disease ◽  
Graft Versus Host ◽  
Clinical Advances ◽  
Acute Graft

Acute graft-versus-host disease (aGvHD) is induced by immunocompetent alloreactive T lymphocytes in the donor graft responding to polymorphic and non-polymorphic host antigens and causing inflammation in primarily the skin, gastrointestinal tract and liver. aGvHD remains an important toxicity of allogeneic transplantation, and the search for better prophylactic and therapeutic strategies is critical to improve transplant outcomes. In this review, we discuss the significant translational and clinical advances in the field which have evolved based on a better understanding of transplant immunology. Prophylactic advances have been primarily focused on the depletion of T lymphocytes and modulation of T-cell activation, proliferation, effector and regulatory functions. Therapeutic strategies beyond corticosteroids have focused on inhibiting key cytokine pathways, lymphocyte trafficking, and immunologic tolerance. We also briefly discuss important future trends in the field, the role of the intestinal microbiome and dysbiosis, as well as prognostic biomarkers for aGvHD which may improve stratification-based application of preventive and therapeutic strategies.

scholarly journals Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1874 ◽  
Author(s):  
Angela Horvath ◽  
Marija Durdevic ◽  
Bettina Leber ◽  
Katharina di Vora ◽  
Florian Rainer ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Controlled Trial ◽  
16S Rrna Gene Sequencing ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Microbiome Composition ◽  
Beneficial Effects ◽  
Compensated Cirrhosis ◽  
Gut Barrier Function ◽  
Probiotic Treatment

Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.

scholarly journals Lyophilized Fecal Microbiota Transplantation Capsules for Recurrent Clostridium difficile Infection

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S381-S381
Author(s):  
Hebert Dupont ◽  
Zhi-Dong Jiang ◽  
Ashley Alexander ◽  
Nadim Ajami ◽  
Joseph F Petrosino ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gene Profiling ◽  
Intestinal Microbiome ◽  
Published Data ◽  
Rrna Gene ◽  
Second Phase ◽  
Microbiome Diversity

Abstract Background Fecal microbiota (FM) transplantation (FMT) is a highly effective treatment of recurrent C. difficile infection (rCDI). We have published data showing efficacy of fresh, frozen and lyophilized donor microbiota administered by colonoscopy. Most groups are moving toward use of frozen product given by enema and in evaluating encapsulated product for oral delivery. Methods This was a prospective, randomized study of subjects with rCDI (≥ 3 episodes) treated with encapsulated lyophilized FM 100 g given once or 100 g given on two successive days (total 200 g) vs. frozen FM product 100 g given by single retention enema, between March 2015 and February 2017. The clinical outcome was absence of CDI during the 60 days after FMT. The subjects were followed for 6 months for safety. In a subset recipients, microbiome composition by 16S rRNA gene profiling were analyzed on stools obtained pre- and day 2, 7, 14, 30, 60 and 90 days after FMT. Results A total of 54 subjects were enrolled (37/54; 69% female) with a median age of 71 years (range: 20–97). In the first 14 subjects treated, cure rates for oral capsules 100 g FM was 5/8 (63%) vs. 6/6 (100%) for those receiving 100 g frozen FM by enema (P = 0.209). In the second phase of the study cure rate for oral capsules 200 g FM was 17/18 (91%) vs. 20/21 (94%) for the subjects treated by enema by 100 g of frozen product (P = 0.782). No side effects were felt to be related to the procedure or the FMT products were recorded during 6 months follow-up. Two subjects died during follow-up between 3 and 6 months after study due to underlying medical conditions felt to be unrelated to FMT. Microbiota analysis were performed on 40 subjects of which 19/40 (48%) had received capsules. Figure showed that restoration of the intestinal microbiome diversity and Taxa began apparent by 2 days after FMT in both groups and resembled the donor product by 2 weeks with stabilization of the microbiota diversity and Taxa persisting for the 90 days of observation. Conclusion Administration of encapsulated, lyophilized FM resulted in durable restoration of intestinal microbiome diversity comparable to results seen with frozen product given by enema. Disclosures All authors: No reported disclosures.

Sign in / Sign up

Export Citation Format

Share Document