Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature
Kamal Srivastava, Mingzhuo Cao, Özkan Fidan, Yanmei Shi, Nan Yang, Anna Nowak‐Węgrzyn, Mingsan Miao, Jixun Zhan, Hugh A. Sampson, Xiu-Min Li
Abstract
Background Gut 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. Objective We 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. Methods Peanut-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. Results BNP 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. Conclusions BNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature.