In vivo Trial of Bifidobacterium longum Revealed the Complex Network Correlations Between Gut Microbiota and Health Promotional Effects

You-Tae Kim; Chul-Hong Kim; Joon-Gi Kwon; Jae Hyoung Cho; Young-Sup Shin; Hyeun Bum Kim; Ju-Hoon Lee

doi:10.3389/fmicb.2022.886934

In vivo Trial of Bifidobacterium longum Revealed the Complex Network Correlations Between Gut Microbiota and Health Promotional Effects

Front Microbiol. 2022 Jun 17:13:886934. doi: 10.3389/fmicb.2022.886934. eCollection 2022.

Authors

You-Tae Kim^{1

2

3

4}, Chul-Hong Kim^{5

6}, Joon-Gi Kwon^{1

2

3

4}, Jae Hyoung Cho⁷, Young-Sup Shin⁶, Hyeun Bum Kim⁷, Ju-Hoon Lee^{1

2

3

4}

Affiliations

¹ Department of Food and Animal Biotechnology, Seoul National University, Seoul, South Korea.
² Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
³ Center for Food and Bioconvergence, Seoul National University, Seoul, South Korea.
⁴ Research Institute of Agriculture and Life Science, Seoul National University, Seoul, South Korea.
⁵ Department of Food Science and Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin, South Korea.
⁶ Food Research Center, Binggrae Co., Ltd., Namyangju, South Korea.
⁷ Department of Animal Resources Science, Dankook University, Cheonan, South Korea.

Abstract

Complete genome sequence analysis of Bifidobacterium longum subsp. longum BCBL-583 isolated from a Korean female fecal sample showed no virulence factor or antibiotic resistance gene, suggesting human safety. In addition, this strain has oxygen and heat tolerance genes for food processing, and cholesterol reduction and mucin adhesion-related genes were also found. For in vivo evaluations, a high fat diet (HFD) mouse model was used, showing that BCBL-583 administration to the model (HFD-583) reduced the total cholesterol and LDL-cholesterol in the blood and decreased pro-inflammatory cytokines but increased anti-inflammatory cytokines, substantiating its cholesterol reduction and anti-inflammation activities. Subsequent microbiome analysis of the fecal samples from the HFD mouse model revealed that BCBL-583 administration changed the composition of gut microbiota. After 9 weeks feeding of bifidobacteria, Firmicutes, Actinobacteria, and Bacteroidetes increased, but Proteobacteria maintained in the HFD mouse models. Further comparative species-level compositional analysis revealed the inhibitions of cholesterol reduction-related Eubacterium coprostanoligenes and obesity-related Lactococcus by the supplementation of B. longum BCBL-583, suggesting its possible cholesterol reduction and anti-obesity activities. The correlation analysis of HFD-583 between the gut microbiota compositional change and cholesterol/immune response showed that Verrucomicrobia, Firmicutes, Actinobacteria, and Bacteroidetes may play an important role in cholesterol reduction and anti-inflammation. However, correlation analysis of Proteobacteria showed the reverse correlation in HFD-583. Interestingly, the correlation analysis of B. longum ATCC 15707 administration to HFD model showed similar patterns of cholesterol but different in immune response patterns. Therefore, this correlation analysis suggests that the microbial composition and inflammatory cytokine/total-cholesterol may be closely related in the administration of BCBL-583 in the HFD mice group. Consequently, BCBL-583 could be a good probiotic strain for gut health promotion through gut microbiota modulation.

Keywords: Bifidobacterium longum; anti-inflammation; cholesterol reduction; gut microbiota; obesity.