Lactobacillus acidophilus and HKL Suspension Alleviates Ulcerative Colitis in Rats by Regulating Gut Microbiota, Suppressing TLR9, and Promoting Metabolism

Abstract

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with complex pathogenesis. The intestinal flora disturbance affects the homeostasis of the intestinal environment, leading to metabolic imbalance and immune abnormalities of the host, contributing to the perpetuation of intestinal inflammation. We suggest that the combination of anti-inflammatory therapy and the regulation of intestinal flora balance may help in the treatment process. Previously, we used a combination treatment consisting of Lactobacillus acidophilus (Lac) and Chinese medicine Huan Kui Le (HKL) suspension in a UC rat model, where the combined intervention was more effective than either treatment alone. Herein, the mechanism of action of this combined treatment has been investigated using 16S rRNA sequencing, immunohistochemistry, and ELISA methods in the colon, and untargeted metabolomics profiling in serum. Colon protein expression levels of IL-13 and TGF-β were upregulated, whereas those of TLR9 and TLR4 were downregulated, consistent with an anti-inflammatory effect. In addition, gut microbiota structure changed, shown by a decrease in opportunistic pathogens correlated with intestinal inflammation, such as Klebsiella and Escherichia-Shigella, and an increase in beneficial bacteria such as Bifidobacterium. The latter correlated positively with IL-13 and TGF-β and negatively with IFN-γ. Finally, this treatment alleviated the disruption of the metabolic profile observed in UC rats by increasing short-chain fatty acid (SCFA)–producing bacteria in the colonic epithelium. This combination treatment also affected the metabolism of lactic acid, creatine, and glycine and inhibited the growth of Klebsiella. Overall, we suggest that treatment combining probiotics and traditional Chinese medicine is a novel strategy beneficial in UC that acts by modulating gut microbiota and its metabolites, TLR9, and cytokines in different pathways.

Ethanol Extract of Limonium bicolor Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis by Alleviating Inflammation and Restoring Gut Microbiota Dysbiosis in Mice

“…Increasing the abundance of g_Akkermansia can decrease the DAI score, restore mucosal architecture, and inhibit the release of pro-inflammatory cytokines in mice with DSS-induced UC, suggesting that g_Akkermansia holds substantial promise as a novel probiotic [34,35]. As one of the most well-known probiotics, g_Lactobacillus protects intestinal barrier function and mucosal immunity by increasing the thickness of the colonic mucosa [36][37][38][39]. In addition, it can alleviate UC by increasing the expression of TLR4/NF-κB, IL-22, and other immune-related genes, restoring intestinal mucosal barrier function, modulating gut microbiota dysbiosis, and inhibiting the growth of pathogenic bacteria [40][41][42].…”

“…Adhesion of microbes to intestinal epithelial cells (ECs) is key to inducing Th17 cells. p_Proteobacteria can adhere to the intestinal epithelium and promote the release of IFN-γ by inducing Th1 cells under the recognition of TLR9 [38,46]. This phenomenon may be one of the reasons for the imbalance of cytokines in UC.…”

Metabolomics meets systems immunology

“…Untargeted metabolomics can reveal important biological associations in immunology research and identify novel metabolites/biomarkers specific to a disease (Ding et al , 2021b ; Alboniga et al , 2022 ; Aximujiang et al , 2022 ; Chen et al , 2022 ; Tian et al , 2022 ). For example, Zhu et al ( 2022 ) used high‐resolution untargeted metabolomics analysis to study influenza A virus subtype H1N1 (H1N1) infected patients and found an association between abnormal arginine metabolism produced by the virus and the immunity of the respiratory mucosa.…”

“…This approach is currently widely used in the discovery of biomarkers, disease diagnosis, and mechanism research, and it provides new insights into the complex study of disease mechanisms (Haimerl et al, 2021;Krishnan et al, 2021;Roberts et al, 2021;Choueiry et al, 2022). Untargeted metabolomics can reveal important biological associations in immunology research and identify novel metabolites/biomarkers specific to a disease (Ding et al, 2021b;Alboniga et al, 2022;Aximujiang et al, 2022;Chen et al, 2022;Tian et al, 2022). For example, Zhu et al (2022) used high-resolution untargeted metabolomics analysis to study influenza A virus subtype H1N1 (H1N1) infected patients and found an association between abnormal arginine metabolism produced by the virus and the immunity of the respiratory mucosa.…”

Gut microbiota: A novel and potential target for radioimmunotherapy in colorectal cancer

“…Lactobacillus and Bifidobacterium suppress animal enteritis by reducing TNF-α by TLR4 ( 39 ). It has been shown that the promotion of IFN-γ release via TLR9 by S. amoebae may contribute to cytokine imbalance in UC ( 40 ). Abnormal TLR signaling activation in immune cells may also lead to the release of pro-inflammatory cytokines, resulting in acute or chronic intestinal inflammation ( 41 ).Additionally, TLRs, activated by microbiota, can also start adaptive immune responses.…”