scholarly journals Prebiotic Supplementation During Gestation Induces a Tolerogenic Environment and a Protective Microbiota in Offspring Mitigating Food Allergy

2022 ◽  
Vol 12 ◽  
Author(s):  
Amandine Selle ◽  
Carole Brosseau ◽  
Wieneke Dijk ◽  
Angéline Duval ◽  
Grégory Bouchaud ◽  
...  
Keyword(s):  
Food Allergy ◽  
Gut Microbiota ◽  
Immune Cell ◽  
Fecal Microbiota ◽  
Epithelial Barrier ◽  
Wheat Allergy ◽  
Immune Cell Subsets ◽  
Attractive Option ◽  
Nutritional Strategies ◽  
The Ideal

Food allergy is associated with alterations in the gut microbiota, epithelial barrier, and immune tolerance. These dysfunctions are observed within the first months of life, indicating that early intervention is crucial for disease prevention. Preventive nutritional strategies with prebiotics are an attractive option, as prebiotics such as galacto-oligosaccharides and inulin can promote tolerance, epithelial barrier reinforcement, and gut microbiota modulation. Nonetheless, the ideal period for intervention remains unknown. Here, we investigated whether galacto-oligosaccharide/inulin supplementation during gestation could protect offspring from wheat allergy development in BALB/cJRj mice. We demonstrated that gestational prebiotic supplementation promoted the presence of beneficial strains in the fecal microbiota of dams during gestation and partially during mid-lactation. This specific microbiota was transferred to their offspring and maintained to adulthood. The presence of B and T regulatory immune cell subsets was also increased in the lymph nodes of offspring born from supplemented mothers, suggestive of a more tolerogenic immune environment. Indeed, antenatal prebiotic supplementation reduced the development of wheat allergy symptoms in offspring. Our study thus demonstrates that prebiotic supplementation during pregnancy induces, in the offspring, a tolerogenic environment and a microbial imprint that mitigates food allergy development.

scholarly journals Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Xuelian Tang ◽  
Weijun Wang ◽  
Gaichao Hong ◽  
Caihan Duan ◽  
Siran Zhu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Epithelial Barrier ◽  
16S Rrna Analysis ◽  
New Strategy

Abstract Background and aims Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. Methods Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. Results The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria—Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. Conclusion Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

scholarly journals Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eric R. Littmann ◽  
Jung-Jin Lee ◽  
Joshua E. Denny ◽  
Zahidul Alam ◽  
Jeffrey R. Maslanka ◽  
...  
Keyword(s):  
T Regulatory Cells ◽  
Immune Cell ◽  
Fecal Microbiota Transplantation ◽  
Critical Role ◽  
Fecal Microbiota ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
Immune Cell Subsets ◽  
Clostridioides Difficile Infection ◽  
Acid Metabolites

AbstractFecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1−/− mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4+ Foxp3+ T-regulatory cells, but not B cells or CD8+ T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host’s inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.

scholarly journals Relationships between Gut Microbiota, Metabolome, Body Weight, and Glucose Homeostasis of Obese Dogs Fed with Diets Differing in Prebiotic and Protein Content

2020 ◽  
Vol 8 (4) ◽  
pp. 513 ◽  
Author(s):  
Emmanuelle Apper ◽  
Lisa Privet ◽  
Bernard Taminiau ◽  
Cindy Le Bourgot ◽  
Ljubica Svilar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Glucose Homeostasis ◽  
Energy Homeostasis ◽  
Latin Square ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Protein Levels ◽  
16S Rrna Amplicon Sequencing ◽  
Metabolic Dysfunctions ◽  
Nutritional Strategies

Obesity is a major issue in pets and nutritional strategies need to be developed, like promoting greater protein and fiber intake. This study aimed to evaluate the effects of dietary protein levels and prebiotic supplementation on the glucose metabolism and relationships between the gut, microbiota, metabolome, and phenotype of obese dogs. Six obese Beagle dogs received a diet containing 25.6% or 36.9% crude protein, with or without 1% short-chain fructo-oligosaccharide (scFOS) or oligofructose (OF), in a Latin-square study design. Fecal and blood samples were collected for metabolite analysis, untargeted metabolomics, and 16S rRNA amplicon sequencing. A multi-block analysis was performed to build a correlation network to identify relationships between fecal microbiota, metabolome, and phenotypic variables. Diets did not affect energy homeostasis, but scFOS supplementation modulated fecal microbiota composition and induced significant changes of the fecal metabolome. Bile acids and several amino acids were related to glucose homeostasis while specific bacteria gathered in metavariables had a high number of links with phenotypic and metabolomic parameters. It also suggested that fecal aminoadipate and hippurate act as potential markers of glucose homeostasis. This preliminary study provides new insights into the relationships between the gut microbiota, the metabolome, and several phenotypic markers involved in obesity and associated metabolic dysfunctions.

Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

Science ◽  
2020 ◽  
pp. eabb5920
Author(s):  
Erez N. Baruch ◽  
Ilan Youngster ◽  
Guy Ben-Betzalel ◽  
Rona Ortenberg ◽  
Adi Lahat ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Cell ◽  
Fecal Microbiota Transplantation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Complete Response ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Clinical Responses ◽  
Melanoma Patients

The gut microbiome has been shown to influence the response of tumors to anti-PD-1 immunotherapy in pre-clinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. Here we performed a phase I clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in ten patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. Together, these early findings have important implications for modulating the gut microbiota in cancer treatment.

scholarly journals Virulent Bacteria as Inflammatory and Immune Co-Factor in Colon Carcinogenesis: Evidence From Two Monozygotic Patients and Validation in CRC Patient and Healthy Cohorts

2021 ◽  
Vol 11 ◽  
Author(s):  
Iradj Sobhani ◽  
Emma Bergsten ◽  
Cecile Charpy ◽  
Mathias Chamaillard ◽  
Denis Mestivier
Keyword(s):  
Gut Microbiota ◽  
Immune Cell ◽  
Bacterial Species ◽  
Monozygotic Twin ◽  
Fecal Microbiota ◽  
Common Disease ◽  
Novel Approach ◽  
Dna Alterations ◽  
Health And Disease ◽  
Immune Tolerant

Colorectal carcinoma (CRC) is a common disease, the incidence of which is increasing according to Western lifestyle; it remains to have a poor prognosis. Western nutriments are presumed to induce mild inflammation within the colonic mucosa, resulting in the accumulation of DNA alterations in colonocytes through a multistage carcinogenesis process. This suggests that most CRCs are related to the environment. Of interest, fecal microbiota composition has been shown yielding a novel approach regarding how environment changes may impact health and disease. Here, we compare whole shotgun metagenomic gut microbiota of two monozygotic twin sisters, one of whom is suffering from an advance colorectal tumor with a profound disequilibrium of the composition of the gut microbiota due to the overexpression of virulent bacteria such as E. coli, Shigella, and Clostridium species in the colon cancer patient’s feces contrasting with low levels of bacterial species such as Faecalibacterium and Akkermansia usually enriched in the healthy adults’ microbial flora. The disequilibrium in microbiota of the CRC patient’s feces as compared to her monozygotic twin sister is linked to inflammatory and immune cell infiltrates in the patient’s colonic tissue. We speculate on the role of microbiota disequilibrium on the immune-tolerant cell infiltrate within CRCs.

scholarly journals Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice

2020 ◽  
Author(s):  
Yingjie Guo ◽  
Yanan Yu ◽  
Hailong Li ◽  
Xueli Ding ◽  
Xiaoyu Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Serum Levels ◽  
Fecal Microbiota ◽  
Urate Oxidase ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Microbial Composition ◽  
Oxidase Gene ◽  
Inflammatory Parameters

Abstract Purpose Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. Methods KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. Results Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. Conclusions Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

scholarly journals Modulation of Gut Microbiota and Oxidative Status by β-Carotene in Late Pregnant Sows

2020 ◽  
Vol 7 ◽  
Author(s):  
Xupeng Yuan ◽  
Jiahao Yan ◽  
Ruizhi Hu ◽  
Yanli Li ◽  
Ying Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Supplementation ◽  
Basal Diet ◽  
Fecal Microbiota ◽  
Control Group ◽  
Metabolic Activities ◽  
The Impact ◽  
Positive Effect ◽  
Β Carotene

Recent evidences suggest that gut microbiota plays an important role in regulating physiological and metabolic activities of pregnant sows, and β-carotene has a potentially positive effect on reproduction, but the impact of β-carotene on gut microbiota in pregnant sows remains unknown. This study aimed to explore the effect and mechanisms of β-carotene on the reproductive performance of sows from the aspect of gut microbiota. A total of 48 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into three groups (n = 16) and fed with a basal diet or a diet containing 30 or 90 mg/kg of β-carotene from day 90 of gestation until parturition. Dietary supplementation of 30 or 90 mg/kg β-carotene increased the number of live birth to 11.82 ± 1.54 and 12.29 ± 2.09, respectively, while the control group was 11.00 ± 1.41 (P = 0.201). Moreover, β-carotene increased significantly the serum nitric oxide (NO) level and glutathione peroxidase (GSH-Px) activity (P &lt; 0.05). Characterization of fecal microbiota revealed that 90 mg/kg β-carotene increased the diversity of the gut flora (P &lt; 0.05). In particular, β-carotene decreased the relative abundance of Firmicutes including Lachnospiraceae AC2044 group, Lachnospiraceae NK4B4 group and Ruminococcaceae UCG-008, but enriched Proteobacteria including Bilophila and Sutterella, and Actinobacteria including Corynebacterium and Corynebacterium 1 which are related to NO synthesis. These data demonstrated that dietary supplementation of β-carotene may increase antioxidant enzyme activity and NO, an important vasodilator to promote the neonatal blood circulation, through regulating gut microbiota in sows.

scholarly journals Comparative Analysis of Fecal Microbiota of Grazing Mongolian Cattle from Different Regions in Inner Mongolia, China

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1938
Author(s):  
Han Aricha ◽  
Huasai Simujide ◽  
Chunjie Wang ◽  
Jian Zhang ◽  
Wenting Lv ◽  
...  
Keyword(s):  
Community Structure ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Inner Mongolia ◽  
Alpha Diversity ◽  
Fecal Microbiota ◽  
Composition Analysis ◽  
Geographical Factors ◽  
Rrna Sequencing ◽  
Xilingol Grassland

Mongolian cattle from China have strong adaptability and disease resistance. We aimed to compare the gut microbiota community structure and diversity in grazing Mongolian cattle from different regions in Inner Mongolia and to elucidate the influence of geographical factors on the intestinal microbial community structure. We used high throughput 16S rRNA sequencing to analyze the fecal microbial community and diversity in samples from 60 grazing Mongolian cattle from Hulunbuir Grassland, Xilingol Grassland, and Alxa Desert. A total of 2,720,545 high-quality reads and sequences that were 1,117,505,301 bp long were obtained. Alpha diversity among the three groups showed that the gut microbial diversity in Mongolian cattle in the grasslands was significantly higher than that in the desert. The dominant phyla were Firmicutes and Bacteroidetes, whereas Verrucomicrobia presented the highest abundance in the gut of cattle in the Alxa Desert. The gut bacterial communities in cattle from the grasslands versus the Alxa Desert were distinctive, and those from the grasslands were closely clustered. Community composition analysis revealed significant differences in species diversity and richness. Overall, the composition of the gut microbiota in Mongolian cattle is affected by geographical factors. Gut microbiota may play important roles in the geographical adaptations of Mongolian cattle.

scholarly journals Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2096
Author(s):  
Celina L. Szanto ◽  
Annelisa M. Cornel ◽  
Sara M. Tamminga ◽  
Eveline M. Delemarre ◽  
Coco C. H. de Koning ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Nk Cells ◽  
Immune Cell ◽  
High Dose Chemotherapy ◽  
Immune Monitoring ◽  
High Dose ◽  
Effector Cells ◽  
Gm Csf ◽  
Immune Cell Subsets

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.

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