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1.
Front Immunol ; 12: 741371, 2021.
Article in English | MEDLINE | ID: mdl-34650564

ABSTRACT

Delivery by cesarean section (CS) is linked to an increased incidence of food allergies in children and affects early gut microbiota colonization. Furthermore, emerging evidence has connected disordered intestinal microbiota to food allergies. Here, we investigated the impact of CS on a rat model for food allergy to ovalbumin (OVA). Rats delivered by CS were found to be more responsive to OVA sensitization than vaginally born ones, displaying a greater reduction in rectal temperature upon challenge, worse diarrhea, and higher levels of OVA-specific antibodies and histamine. 16S rRNA sequencing of feces revealed reduced levels of Lactobacillus and Bifidobacterium in the CS rats. Preventative supplementation with a probiotic combination containing Lactobacillus and Bifidobacterium could protect CS rats against an allergic response to OVA, indicating that the microbiota dysbiosis contributes to CS-related response. Additionally, probiotic intervention early in life might help to rebuild aberrant Th2 responses and tight junction proteins, both of which have been linked to CS-related high allergic reactions. Taken together, this study shows that disordered intestinal microbiota plays an essential role in the pathogenesis of food allergy mediated by CS. More importantly, interventions that modulate the microbiota composition in early life are therapeutically relevant for CS-related food allergies.


Subject(s)
Bifidobacterium/immunology , Cesarean Section/statistics & numerical data , Dysbiosis/prevention & control , Food Hypersensitivity/prevention & control , Gastrointestinal Microbiome/immunology , Lactobacillus/immunology , Probiotics/administration & dosage , RNA, Ribosomal, 16S/genetics , Th2 Cells/immunology , Allergens/immunology , Animals , Bifidobacterium/genetics , Cells, Cultured , Disease Models, Animal , Female , Food Hypersensitivity/epidemiology , Humans , Immunoglobulin E/blood , Lactobacillus/genetics , Male , Ovalbumin/immunology , Pregnancy , Rats , Rats, Sprague-Dawley , Tight Junctions/metabolism
2.
Front Immunol ; 12: 783806, 2021.
Article in English | MEDLINE | ID: mdl-35116024

ABSTRACT

Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.


Subject(s)
Colitis, Ulcerative/metabolism , Colitis, Ulcerative/microbiology , Colon/metabolism , Gastrointestinal Microbiome/drug effects , Melatonin/metabolism , Melatonin/pharmacology , Animals , Colitis, Ulcerative/chemically induced , Colon/drug effects , Fecal Microbiota Transplantation , Humans , Mice , Oxazolone/toxicity
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