ORIGINAL RESEARCH published: 17 February 2022 doi: 10.3389/fmicb.2022.820236 Edited by: Robert Czajkowski, University of Gda ´ nsk, Poland Reviewed by: Rohit Sharma, Shoolini University of Biotechnology and Management Sciences, India Parisa Gazerani, Oslo Metropolitan University, Norway Guilherme Zweig Rocha, State University of Campinas, Brazil *Correspondence: Yanchun Hu hychun114@163.com Specialty section: This article was submitted to Microbial Symbioses, a section of the journal Frontiers in Microbiology Received: 23 November 2021 Accepted: 04 January 2022 Published: 17 February 2022 Citation: Okyere SK, Wen J, Cui Y, Xie L, Gao P, Zhang M, Wang J, Wang S, Ran Y, Ren Z and Hu Y (2022) Bacillus toyonensis SAU-19 and SAU-20 Isolated From Ageratina adenophora Alleviates the Intestinal Structure and Integrity Damage Associated With Gut Dysbiosis in Mice Fed High Fat Diet. Front. Microbiol. 13:820236. doi: 10.3389/fmicb.2022.820236 Bacillus toyonensis SAU-19 and SAU-20 Isolated From Ageratina adenophora Alleviates the Intestinal Structure and Integrity Damage Associated With Gut Dysbiosis in Mice Fed High Fat Diet Samuel Kumi Okyere 1 , Juan Wen 1 , Yujing Cui 1 , Lei Xie 1 , Pei Gao 1 , Ming Zhang 1 , Jianchen Wang 1 , Shu Wang 1 , Yinan Ran 1 , Zhihua Ren 1 and Yanchun Hu 1,2 * 1 Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China, 2 New Ruipeng Pet Healthcare Group Co., Ltd., Shenzhen, China This study was performed to identify potential probiotic endophytes from Ageratina adenophora and evaluate their ameliorating effects on gut injury and integrity damage associated with microbiota dysbiosis in mice fed high fat diet. Using morphological and biochemical tests, and 16S rRNA gene sequencing technique, two bacteria endophytes were identified as strains of Bacillus toyonensis and were named Bacillus toyonensis SAU-19 (GenBank No. MW287198) and Bacillus toyonensis SAU-20 (GenBank No. MW287199). Sixty (60) mice were divided into five groups, group 1 was the negative control fed normal diet (NS), group 2 was fed High fat diet (HF), Group 3 was fed High fat diet + 10 6 Lactobacillus rhamnosus (LGG), group 4 was fed High fat + 10 6 Bacillus toyonensis SAU-19 and group 5 fed High fat diet + 10 6 Bacillus toyonensis SAU-20. After 35 days, histological and immunohistochemistry examination were performed in the ileum tissues. Furthermore, DAO and antioxidants activities were measured in serum, mRNA expressions of tight junction proteins (occludin and ZO-1) and inflammation related cytokines (IL-1β, TFN-α, IL-2, IL-4, and IL-10) in the ileum tissues as well as sIgA levels and total bacteria (Escherichia coli, Salmonella, Staphylococcus, and Lactobacillus) in the small intestine and cecum content. The results showed an increase in the DAO activity, oxidative stress parameter (MDA), pro-inflammation cytokines (IL- 1β, TFN-α, IL-2), reduce immunity (sIgA), and destroyed intestinal structure and integrity (reduce tight junction proteins) in the high fat diet group and this was associated with destruction of the gut microbiota composition (increasing pathogenic bacteria; E. coli, Salmonella, Staphylococcus and reducing beneficial bacteria, Lactobacillus spp.) in mice (P < 0.05). However, the administration of Bacillus toyonensis SAU-19 and SAU- 20 reverted these effects. Our findings indicated that, Bacillus toyonensis SAU-19 and Frontiers in Microbiology | www.frontiersin.org 1 February 2022 | Volume 13 | Article 820236