Influences of non-IgE-mediated cow's milk protein allergy-associated gut microbial dysbiosis on regulatory T cell-mediated intestinal immune tolerance and homeostasis

Wang, Jinzhi; Zheng, Shuang; Yang, Xin; Huazeng, Ben; Qian, Cheng

doi:10.1016/j.micpath.2021.105020

Cited by 16 publications

(32 citation statements)

References 60 publications

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“…The intestinal Treg response is crucial in the development of oral tolerance and protection against IgE-mediated food allergies. 41 Increased CD4 + CD25 + Foxp3 + Treg frequency in the spleen indicates alleviated symptoms of allergic reaction, 42 and we observed similar findings in the FA mice upon MALAT1 downregulation. Reduced expression of Foxp3, IL-10, and TGF-β represents weakened suppressive activity of Tregs and the opposite represents enhancement.…”

Section: Discussionsupporting

confidence: 77%

MALAT1 Induces Food Allergy by Promoting Release of IL-6 from Dendritic Cells and Suppressing the Immunomodulatory Function of Tregs

Feng¹,

Xiong²,

Chen³

et al. 2022

JAA

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Background Dendritic cells (DCs) comprise a valuable target for immune-modulation in food allergy (FA). Long noncoding RNA (lncRNA), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has immunomodulatory capacities and may influence the outcome of DC antigen presentation. However, the precise molecular mechanisms underlying the implication of MALAT1 in FA remain unclear. Methods BALB/c mice were sensitized to ovalbumin in accordance with a model of FA protocol and injected with adenovirus. After modeling, immunohistochemistry was performed to analyze the jejunal tissues of FA mice and hematoxylin-eosin staining and toluidine blue staining were performed to detect inflammation and mast cell numbers. Ovalbumin-sensitized mice were monitored for symptoms of diarrhea and rectal temperature. Immature DCs were stimulated by oxidized low density lipoprotein to trigger their maturation. Results MALAT1 was found highly expressed in mice with FA, and its silencing relieved allergic reactions with reduction in intestinal inflammatory cells and mast cells in FA mice. MALAT1 aggravated symptoms by downregulating zinc finger protein 36 (ZFP36). MALAT1 also downregulated ZFP36 expression to promote interleukin-6 (IL-6) secretion by DCs and maturation of DCs, with increased serum-specific immunoglobulin E (IgE) and IgG1 levels. Conclusion Together, these data suggested that therapeutically blocking MALAT1 in FA could reduce the severity of FA by decreasing secretion of IL-6 by DCs and suppressing the immunomodulation of Tregs.

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Section: Discussionsupporting

confidence: 77%

MALAT1 Induces Food Allergy by Promoting Release of IL-6 from Dendritic Cells and Suppressing the Immunomodulatory Function of Tregs

Feng¹,

Xiong²,

Chen³

et al. 2022

JAA

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“…The included studies were conducted between 2014–2021. Three of the included studies were conducted in North America [ 19 , 20 , 21 ], two in Europe [ 22 , 23 ], one in the Middle East [ 24 ], five in East Asia [ 25 , 26 , 27 , 28 , 29 ] and one in the United States/Italy [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…Of the 12 included articles, 11 studies reported results on gut microbiota differences between children with FAs compared to an HC group [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. All participants were under the age of 18 years, with most being infants.…”

Section: Resultsmentioning

confidence: 99%

“…All studies excluded children who had used antibiotics and pre- or probiotics during the weeks before fecal sampling. The mode of delivery varied, but some studies reported that children born prematurely were excluded [ 19 , 21 , 26 , 28 ]. Four studies excluded children with chronic inflammatory diseases, autoimmune diseases and metabolic diseases [ 19 , 22 , 24 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

“…The mode of delivery varied, but some studies reported that children born prematurely were excluded [ 19 , 21 , 26 , 28 ]. Four studies excluded children with chronic inflammatory diseases, autoimmune diseases and metabolic diseases [ 19 , 22 , 24 , 28 ]. Dong et al [ 25 ] only included breastfed infants, whereas others included formula-fed [ 28 ] or both [ 19 , 20 , 21 , 22 , 23 , 26 , 27 ].…”

Section: Resultsmentioning

confidence: 99%

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Gut Microbiota and Fecal Microbiota Transplantation in Patients with Food Allergies: A Systematic Review

2022

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The prevalence of food allergies (FAs) has increased considerably in recent decades, with the only available treatment being the avoidance of the specific food items causing the allergy. FAs may have a major impact on quality of life, and it is of great interest to explore new strategies to prevent and treat FAs. Some studies show an altered gut microbiota profile in individuals with FAs, and the modulation of gut microbiota is therefore proposed as a potential strategy for prevention and treatment. This systematic review aimed to investigate: (1) the gut microbiota profile in individuals with FAs compared to healthy individuals and (2) the effect of fecal microbiota transplantation (FMT) on gut microbiota profiles and/or allergy symptoms. A literature search was conducted in PubMed (Medline) on 5 April 2022. Of the 236 publications identified, 12 studies were included based on inclusion and exclusion criteria. Eleven of these studies reported results on the gut microbiota in children with FAs compared to healthy controls (HCs). The majority of studies (six studies) observed no difference in alpha diversity when comparing children with FAs to HCs; however, a difference in beta diversity was observed in five studies. At the phylum level, we observed a high abundance of Firmicutes (six studies) and Proteobacteria (five studies), whereas a low abundance of Bacteroidetes (5 studies) was observed in children with FAs compared to HCs. Of the 12 included studies, four explored the effect of FMT on gut microbiota and/or allergy symptoms. Three studies reported that transferring gut microbiota from children without FAs to germ-free mice, protected the mice against allergic reactions, whereas one study did not report findings on the allergic symptoms. The results on gut microbiota after FMT varied and were too divergent to draw any conclusions. Overall, our results suggest that there are differences in the gut microbiota profile in individuals with FAs compared to individuals without FAs. FMT seems to be a promising strategy to prevent allergic symptoms but needs to be further explored in animal and human models. As the findings in this review are based on a small number of studies (12 studies), further studies are warranted before any clear conclusions can be drawn regarding gut microbiota profiles and the effect of FMT on individuals with FAs.

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Gut microbiota and inflammatory mediators differentiate IgE mediated and non‐IgE mediated cases of cow's milk protein at diagnosis

Castro,

Gutiérrez‐Díaz,

Saiz

et al. 2024

J. pediatr. gastroenterol. nutr.

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ObjectiveAnalyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non‐IgE mediated (NIM)‐CMPA patients to look for potential new biomarkers.Patients and MethodsFourteen patients with IgE mediated CMPA and 13 with NIM‐CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme‐linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry.ResultsThe fecal results obtained in the NIM‐CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL‐10 and a lower excretion of IL‐1ra and platelet derived growth factor‐BB was found in NIM‐CMPA patients.ConclusionsThe differential fecal parameters found in NIM‐CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

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Influences of non-IgE-mediated cow's milk protein allergy-associated gut microbial dysbiosis on regulatory T cell-mediated intestinal immune tolerance and homeostasis

Cited by 16 publications

References 60 publications

MALAT1 Induces Food Allergy by Promoting Release of IL-6 from Dendritic Cells and Suppressing the Immunomodulatory Function of Tregs

MALAT1 Induces Food Allergy by Promoting Release of IL-6 from Dendritic Cells and Suppressing the Immunomodulatory Function of Tregs

Gut Microbiota and Fecal Microbiota Transplantation in Patients with Food Allergies: A Systematic Review

Gut microbiota and inflammatory mediators differentiate IgE mediated and non‐IgE mediated cases of cow's milk protein at diagnosis

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