Contribution of Gut Microbiota to Immune Tolerance in Infants

The prevalence of food allergy has increased in recent years, especially among the pediatric population. Differences in the gut microbiota composition between children with FA and healthy children have brought this topic into the spotlight as a possible explanation for the increase in FA. The gut microbiota characteristics are acquired through environmental interactions starting early in life, such as type of delivery during birth and breastfeeding. The microbiota features may be shaped by a plethora of immunomodulatory mechanisms, including a predominant role of Tregs and the transcription factor FOXP3. Additionally, a pivotal role has been given to vitamin A and butyrate, the main anti-inflammatory metabolite. These observations have led to the study and development of therapies oriented to modifying the microbiota and metabolite profiles, such as the use of pre- and probiotics and the determination of their capacity to induce tolerance to allergens that are relevant to FA. To date, evidence supporting these approaches in humans is scarce and inconclusive. Larger cohorts and dose-titration studies are mandatory to evaluate whether the observed changes in gut microbiota composition reflect medical recovery and increased tolerance in pediatric patients with FA. In this article, we discuss the establishment of the microbiota, the immunological mechanisms that regulate the microbiota of children with food allergies, and the evidence in research focused on its regulation as a means to achieve tolerance to food allergens.

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Microbial signature in IgE-mediated food allergies

Genome Medicine ◽

10.1186/s13073-020-00789-4 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Michael R. Goldberg ◽

Hadar Mor ◽

Dafna Magid Neriya ◽

Faiga Magzal ◽

Efrat Muller ◽

...

Keyword(s):

Food Allergy ◽

Gut Microbiota ◽

Learning Algorithm ◽

Area Under The Curve ◽

Food Allergies ◽

Rrna Gene ◽

Microbiota Composition ◽

Α Diversity ◽

Ige Mediated ◽

Gut Microbiota Composition

Abstract Background Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. Methods To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31). Results The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. Conclusions Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.

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The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome

Nutrients ◽

10.3390/nu13113836 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3836

Author(s):

Cristina Iribarren ◽

Maria K. Magnusson ◽

Louise K. Vigsnæs ◽

Imran Aziz ◽

Ingvild Dybdrodt Amundsen ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Human Milk ◽

Microbiota Composition ◽

Bifidobacterium Adolescentis ◽

Metabolite Profiles ◽

Mucosal Response ◽

Irritable Bowel ◽

Plasma Metabolite ◽

Gut Microbiota Composition

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

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Prebiotic supplementation over a cold season and during antibiotic treatment specifically modulates the gut microbiota composition of 3-6 year-old children

Beneficial Microbes ◽

10.3920/bm2018.0116 ◽

2019 ◽

Vol 10 (3) ◽

pp. 253-263 ◽

Cited By ~ 7

Author(s):

S. Soldi ◽

S. Vasileiadis ◽

S. Lohner ◽

F. Uggeri ◽

E. Puglisi ◽

...

Keyword(s):

Gut Microbiota ◽

Antibiotic Treatment ◽

Relative Abundance ◽

Cold Season ◽

Medical Attention ◽

Control Group ◽

Rrna Gene ◽

Healthy Children ◽

Microbiota Composition ◽

Gut Microbiota Composition

Supplementing kindergarten children during a cold season with a prebiotic inulin-type fructans product with shorter and longer fructan chains has been shown to reduce febrile episodes requiring medical attention and to lower the incidence of sinusitis. These beneficial effects may be connected to the specific modulation of children’s gut microbiota. By applying quantitative and qualitative microbiota analysis this study aimed at characterising the gut microbiota composition and at exploring effects of prebiotic intervention on the gut microbiota during a 24-weeks intervention and during antibiotic treatment in healthy children. The study was a randomised, placebo-controlled trial with 258 healthy children aged 3 to 6 years consuming 6 g/day prebiotic inulin-type fructans or maltodextrin. During the course of the study, faecal samples were collected and subject to targeted qPCR analysis and phylogenetic profiling by multiplexed high throughput sequencing of the prokaryotic 16S rRNA gene PCR amplicons. The microbiota composition of the cohort could be clustered into three distinct constellations (enterotypes). Prebiotic intake resulted in a selective modulation of the gut microbiota composition. Relative abundance of Bifidobacterium was significantly higher in the prebiotic group (n=104) compared to control group (n=105) and this effect was found for all three enterotypes. Antibiotic administration decreased the relative abundance of Bifidobacterium in both groups. Nonetheless, children of the prebiotic group receiving antibiotic treatment displayed significantly higher levels of Bifidobacterium than children receiving the placebo control. Prebiotic supplementation induced specific changes in the gut microbiota composition of children aged 3 to 6 years. Moreover, it attenuated antibiotic-induced disturbances in the gut microbiota composition as shown by higher relative abundance of bifidobacteria at the end of the antibiotic treatment in the prebiotic group. With the previously reported benefits on immune function, the study contributes to the evidence on the immune-modulating effects of prebiotics through gut microbiota modifications. The study was registered as NCT03241355 ( https://clinicaltrials.gov/show/NCT03241355 ).

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Oral Administration ofPorphyromonas gingivalisAlters the Gut Microbiome and Serum Metabolome

mSphere ◽

10.1128/msphere.00460-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 27

Author(s):

Tamotsu Kato ◽

Kyoko Yamazaki ◽

Mayuka Nakajima ◽

Yasuhiro Date ◽

Jun Kikuchi ◽

...

Keyword(s):

Gut Microbiota ◽

Periodontal Disease ◽

Oral Administration ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Microbiota Composition ◽

Content Type ◽

Increased Risk ◽

Metabolite Profiles ◽

Gut Microbiota Composition

ABSTRACTPeriodontal disease induced by periodontopathic bacteria likePorphyromonas gingivalisis demonstrated to increase the risk of metabolic, inflammatory, and autoimmune disorders. Although precise mechanisms for this connection have not been elucidated, we have proposed mechanisms by which orally administered periodontopathic bacteria might induce changes in gut microbiota composition, barrier function, and immune system, resulting in an increased risk of diseases characterized by low-grade systemic inflammation. Accumulating evidence suggests a profound effect of altered gut metabolite profiles on overall host health. Therefore, it is possible thatP. gingivaliscan affect these metabolites. To test this, C57BL/6 mice were administered withP. gingivalisW83 orally twice a week for 5 weeks and compared with sham-inoculated mice. The gut microbial communities were analyzed by pyrosequencing the 16S rRNA genes. Inferred metagenomic analysis was used to determine the relative abundance of KEGG pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance (NMR)-based metabolomics coupled with multivariate statistical analyses. Oral administration ofP. gingivalisinduced a change in gut microbiota composition. The distributions of metabolic pathways differed between the two groups, including those related to amino acid metabolism and, in particular, the genes for phenylalanine, tyrosine, and tryptophan biosynthesis. Also, alanine, glutamine, histidine, tyrosine, and phenylalanine were significantly increased in the serum ofP. gingivalis-administered mice. In addition to altering immune modulation and gut barrier function, oral administration ofP. gingivalisaffects the host’s metabolic profile. This supports our hypothesis regarding a gut-mediated systemic pathology resulting from periodontal disease.IMPORTANCEIncreasing evidence suggest that alterations of the gut microbiome underlie metabolic disease pathology by modulating gut metabolite profiles. We have shown that orally administeredPorphyromonas gingivalis, a representative periodontopathic bacterium, alters the gut microbiome; that may be a novel mechanism by which periodontitis increases the risk of various diseases. Given the association between periodontal disease and metabolic diseases, it is possible thatP. gingivaliscan affect the metabolites. Metabolite profiling analysis demonstrated that several amino acids related to a risk of developing diabetes and obesity were elevated inP. gingivalis-administered mice. Our results revealed that the increased risk of various diseases byP. gingivalismight be mediated at least in part by alteration of metabolic profiles. The findings should add new insights into potential links between periodontal disease and systemic disease for investigators in periodontal disease and also for investigators in the field of other diseases, such as metabolic diseases.

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Differences in Manifestations and Gut Microbiota Composition Between Patients With Different Henoch-Schonlein Purpura Phenotypes

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.641997 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yuanzhen Zhang ◽

Guizhi Xia ◽

Xiaojing Nie ◽

Yugui Zeng ◽

Yi Chen ◽

...

Keyword(s):

Gut Microbiota ◽

Complement C3 ◽

Control Group ◽

Healthy Children ◽

Microbiota Composition ◽

Henoch Schonlein Purpura ◽

Abdominal Symptoms ◽

Schonlein Purpura ◽

Gut Microbiota Composition ◽

Henoch Schönlein Purpura

BackgroundGut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP.Methods16SrRNA gene sequencing and bioinformatic analyses were performed using total DNA extracted from the fecal microbiota of 34 children with HSP, including 18 primary cases, 16 recurrent cases, and 23 healthy children.ResultsThe diversity indexes showed significant differences in the microbial community among the primary HSP groups, the recurrent HSP group and healthy controls. The abundance of Escherichia-Shigella in the recurrent HSP group was significantly higher than that in the primary HSP group, and the constructed ROC curve had an AUC value of 0.750. According to the Spearman correlation analysis, the abundance of Bacteroides was positively associated with the serum IgG level in children with HSP, while the abundance of Lachnoclostridium was negatively correlated with the complement component 3 (C3). The diversity indexes of gut microbiota in the HSP group with abdominal symptoms were higher than those in the HSP group without GI involvement, and also higher than those in the healthy control group. In the HSP group with GI involvement, the abundance of Faecalibacterium was decreased, while the abundance of Streptococcus and Fusobacteria was increased, compared to the HSP group without GI involvement.ConclusionsThe gut microbiota of children with HSP was different from that of healthy children. The genus Escherichia-Shigella has a diagnostic value for HSP recurrence. Bacteroides and Lachnoclostridium may affect IgG and complement C3 levels in children with HSP. Abdominal symptoms in HSP children were related to gut microbiota (Streptococcus and butyric acid-producing bacteria).

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