Full
Outline
To investigate the effects of autologous fecal microbiota transplantation (AFMT) on immune regulation and tumor suppression in a murine model of colitis-associated colorectal cancer (CAC) induced by azoxymethane (AOM)/dextran sulfate sodium (DSS), with mechanistic emphasis on NF-κB pathway inhibition and CD8⁺ T cell/regulatory T cell (Treg) balance modulation.
Six-week-old female BALB/c mice [SPF grade, body weight (20±2) g] were randomly divided into 3 groups (n=5 per group): control group (Con), CAC model group (Mod), and AFMT intervention group (AFMT). The CAC model was established by a single intraperitoneal injection of AOM (10 mg/kg) followed by three cycles of DSS treatment (each cycle: 3.5%DSS in drinking water for 7 d plus 14 d of recovery with sterile water). Starting from day 7 post-modeling, the AFMT group received 0.1 mL of autologous fecal microbiota suspension via oral gavage every other day until the end of the experiment; control groups received equal volumes of sterile saline. At endpoint, colorectal tissues, spleen, serum, and fecal samples were collected. Colonic pathological injury and inflammatory cell infiltration were assessed by hematoxylin-eosin (HE) staining. NF-κB p65 and p-NF-κB p65 protein expression in colon tissue was detected by Western blot. Serum TNF-α levels were measured by ELISA. Flow cytometry was used to analyze the proportions of CD8+ T cells and regulatory T cells (Treg, defined as CD4+CD25+Foxp3+) in the spleen. Gut microbiota composition and diversity (α- and β-diversity) were analyzed by 16S rRNA sequencing.
Compared with the Con group, the Mod group showed a reduction in goblet cells and significant inflammatory cell infiltration in HE-stained colon sections, an increased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (P<0.05), elevated serum TNF-α levels (P<0.001), a decreased proportion of CD8⁺ T cells in the spleen (P<0.001), an increased proportion of Treg cells (P<0.05), an increased relative abundance of Bacteroidales (P<0.05), and a decreased relative abundance of Lactobacillales (P<0.05). Compared with the Mod group, the AFMT group showed milder structural damage and reduced inflammatory cell infiltration in the colon, a decreased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (P<0.01), reduced serum TNF-α levels (P<0.01), an increased proportion of CD8⁺ T cells in the spleen (P<0.05), a decreased proportion of Treg cells (P<0.05), a decreased relative abundance of Bacteroidales (P<0.05), and an increased relative abundance of Lactobacillales (P<0.05).
AFMT intervention may alleviate disease progression in CAC model mice through multiple mechanisms: restoring the abundance of Lactobacillales, enhancing the intestinal barrier function and promoting short-chain fatty acid production, inhibiting the NF-κB inflammatory pathway, reducing TNF-α levels, and regulating T-cell immune balance.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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