Browsing by Author "Srivastava, Kamal"

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Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature
(FRONTIERS MEDIA SA, 2023) Srivastava, Kamal; Cao, Mingzhuo; Fidan, Ozkan; Shi, Yanmei; Yang, Nan; Nowak-Wegrzyn, Anna; Miao, Mingsan; Zhan, Jixun; Sampson, Hugh A.; Li, Xiu-Min; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
BackgroundGut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. ObjectiveWe sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes. MethodsPeanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE(+)B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms. ResultsBNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE(+) B cells (p <0.001 vs Sham for all). Significant differences were observed for Firmicutes/Bacteroidetes ratio across treatment groups. Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae, and Hydrogenanaerobacterium (all Firmicutes) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae, and Bacteroidales were negatively correlated. ConclusionsBNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature.
Inhibition of pathologic immunoglobulin E in food allergy by EBF-2 and active compound berberine associated with immunometabolism regulation
(FRONTIERS MEDIA SA, 2023) Yang, Nan; Maskey, Anish R.; Srivastava, Kamal; Kim, Monica; Wang, Zixi; Musa, Ibrahim; Shi, Yanmei; Fidan, Ozkan; Wang, Julie; Dunkin, David; Chung, Danna; Zhan, Jixun; Miao, Mingsan; Sampson, Hugh A; Li, Xiu-Min; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
IntroductionFood allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production. MethodsIgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE(+) plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated. ResultsEBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p<0.001) and the number of IgE-producing plasma cells in PN allergic mice, accompanied by 100% inhibition of PN-induced anaphylaxis and plasma histamine release (p<0.001) without affecting IgG1 or IgG2a production. Berberine markedly suppressed IgE production, which was associated with suppression of XBP1, BLIMP1, and STAT6 transcription factors and a reduced rate of mitochondrial oxidation in an IgE-producing plasma cell line. ConclusionsEBF-2 and its active compound berberine are potent IgE suppressors, associated with cellular regulation of immunometabolism on IgE plasma cells, and may be a potential therapy for IgE-mediated food allergy and other allergic disorders.