Effect of Lactobacillus fermentum ZS40 on the NF-κB signaling pathway in an azomethane-dextran sulfate sodium-induced colon cancer mouse model
- 2022-09-26
- Frontiers in Microbiology 13
- Jia Liu
- Shuaiqi Wang
- Ruokun Yi
- X. Long
- Xin Zhao
- PubMed: 36225358
- DOI: 10.3389/fmicb.2022.953905
Abstract
The occurrence of intestinal diseases such as colon cancer is closely related to the intestinal flora. Lactobacillus fermentum is a gut probiotic that plays an important role in chronic intestinal inflammation and colon cancer. In the current study, we investigated the effect of Lactobacillus fermentum ZS40 on NF-κB signaling pathway of azomethane-dextran sulfate sodium (AOM-DSS) -induced colon cancer in mice. Animals were divided into control group (NC), AOM-DSS-induced model group (CRC), AOM-DSS plus high-dose Lactobacillus fermentum ZS40 (ZS40-H), AOM-DSS plus low-dose Lactobacillus fermentum ZS40 (ZS40-L), AOM-DSS plus Lactobacillus bulgaricus (BLA), and AOM-DSS plus sulfasalazine (SD)-treated group. Observation of animal physiological activity (body weight and defecation), biochemical measurements, histopathological examination of colon tissue, qPCR to evaluate the expression of inflammation-related genes, immunohistochemical analysis of CD34 and CD117, and Western blot analysis of NF-κB signaling pathway were performed. Compared with the CRC group, the ZS40-H, ZS40-L, BLA, and SD groups had decreased levels of colon cancer marker proteins CD34 and CD117, and the number of abnormal colonic lesions observed by colon histology decreased, while the ZS40-H group showed excellent results. In addition, all probiotic interventions showed weight loss effects. The expression of inflammatory stimulators TNF-α and IL-1β in the probiotic treatment group decreased; the expression of key proteins IκBα and p65 in the NF-κB signaling pathway also decreased, resulting in a decrease in the expression of the target protein Cox-2. Therefore, administration of Lactobacillus fermentum ZS40 as a probiotic can alleviate intestinal inflammation and prevent colon cancer in mice.
Keywords: AOM-DSS; Lactobacillus fermentum; NF-κB signaling pathway; colon cancer; inflammation-related genes.
Research Insights
| Supplement | Health Outcome | Effect Type | Effect Size |
|---|---|---|---|
| Lactobacillus fermentum | Reduced Body Weight | Beneficial | Moderate |
| Lactobacillus fermentum | Reduced Incidence of Colon Cancer | Beneficial | Large |
| Lactobacillus fermentum | Reduced Inflammation Levels | Beneficial | Large |
| Lactobacillus fermentum Lf-33 | Reduced Abnormal Colonic Lesions | Beneficial | Large |
| Lactobacillus fermentum Lf-33 | Reduced Activation of TLR4/NF-κB Signaling Pathway | Beneficial | Moderate |
| Lactobacillus fermentum Lf-33 | Reduced Body Weight | Beneficial | Moderate |
| Lactobacillus fermentum Lf-33 | Reduced Colon Cancer Marker Proteins | Beneficial | Large |
| Lactobacillus fermentum Lf-33 | Reduced Inflammatory Stimulators | Beneficial | Large |
| Lactobacillus fermentum LF61 | Inhibited NF-kB Pathway Activation | Beneficial | Large |
| Lactobacillus fermentum LF61 | Reduced Abnormal Colonic Lesions | Beneficial | Large |
| Lactobacillus fermentum LF61 | Reduced Body Weight | Beneficial | Moderate |
| Lactobacillus fermentum LF61 | Reduced Colon Cancer Marker Proteins | Beneficial | Large |
| Lactobacillus fermentum LF61 | Reduced Inflammatory Stimulators | Beneficial | Large |