Bifidobacterium BLa80 mitigates colitis by altering gut microbiota and alleviating inflammation

Background

Inflammatory bowel disease (IBD), whose clinical manifestations include ulcerative colitis (UC), affects the health of the intestinal tract, leads to frequent diarrhea, abdominal cramps, and rectal bleeding. In the past, probiotic strains belonging to Bifidobacterium have been found to have the ability to alleviate the symptoms of IBD, reduce intestinal dysbiosis In this study, we evaluated the ability of strain BLa80 to alleviate Dextran Sulphate Sodium (DSS) - induced colitis in mice.

Methods

 C57BL/6J mice, 10/group, male, 4 weeks old

• BLa80 group: drinking DSS water for the 0th~9th d to induce colitis, 109 CFU BLa80 by gavage daily for the 1st~8th d, stopping gavage for the 9th~12th d and drinking normal water

• UC group: drinking DSS water on the 0th~9th d, gavage of equal amount of saline daily on the 1st~8th d, stop gavage on the 9th~12th d and drinking normal water

• CTL group: drinking normal water for the 0th to 12th d, gavage equal amount of saline every day for the 1st to 8th d

Results

Reduced Colitis Symptoms – Reduced Disease Activity Index (DAI)

Scoring evaluation based on body weight, fecal traits and fecal occult blood (intestinal bleeding) in mice, with higher scores indicating worse conditions

Fig. 1 Effects of BLa80 on body weight, Disease Activity Index Assessment (DAI) (A: weight change; B: DAI score)

The mice in the UC group had significant weight loss, and BLa80 reduced the weight loss; the mice in the UC group had high DAI scores, indicating severe clinical disease manifestations, and BLa80 significantly reduced the DAI scores of the mice

Reduced Colitis Symptoms - Reduced Tissue Damage

Three groups of mouse colons were dissected and observed for changes in length; sections of distal colon tissue were stained and examined under a microscope and scored; higher scores were associated with more inflammatory damage

Fig. 2 Effects of BLa80 on colon length and distal colonic tissue (A: colon length; B: colon tissue score; C: distal colitis tissue)

BLa80 reversed dss-induced colonic shortening, attenuated mucosal inflammation, crypt ulceration and intestinal epithelial layer edema, and attenuated inflammatory score

Reduced the inflammatory response

At the end of the test, the changes of pro-inflammatory cytokines, tumor necrosis factor (TNF-α), interleukin IL-6, and IL-17, in response to inflammation were measured in the serum of the three groups of mice

Fig. 3 Concentrations of TNF-α (A), IL- 6 (B) and IL-17 (C) in mouse sera

BLa80 reduced serum pro-inflammatory cytokine concentrations and alleviates inflammatory manifestations

Microbiota analysis

Mouse colon fecal samples were taken and analyzed by 16S rRNA high-throughput sequencing and macro-genomic analysis to compare the differences in the phylum and genus composition of the bacterial flora of the three groups of mice, and the Shannon index could reflect the community diversity of the bacterial flora, and the Chao index could respond to the community richness of the bacterial flora

Fig. 4 Characterization of intestinal microflora in mice (A: Chao; B: Shannon; C: flora phylum composition)

BLa80 intervention partially restored the alpha diversity of the flora (A/B), and BLa80 ameliorated the increase in the relative abundance of Bacteroidetes, and the decrease in the abundance of Firmicutes

Conclusions

Bifidobacterium animalis subsp. lactis BLa80 can significantly alleviated DSS-induced acute UC symptoms in mice. BLa80 not only alleviated macropathological symptoms (e.g., reduced weight loss, improved disease activity index (DAI), but also improved the inflammatory profile (e.g., alleviated colonic lesions, reduced pro-inflammatory cytokine levels）, which correlation analysis suggested may be caused by BLa80 promoting a improve in the relative abundance of genera such as Romboutsia and Adlercreutzia spp. BLa80 also promoted beneficial genera such as Lactobacillus, E. faecalis, Bifidobacterium, and Ligilactobacillus, and inhibited the colonization of conditionally pathogenic bacteria such as E. coli, Shigella, enhancing the stability of the intestinal microflora

Note: Figures 3/4 are examples of data only, due to space constraints, more data can be found in the original article