Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2025; 31(1): 96199
Published online Jan 7, 2025. doi: 10.3748/wjg.v31.i1.96199
Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats
Ping Zhang, Ying Zhu, Pu Chen, Tong Zhou, Zhe-Yi Han, Jun Xiao, Jian-Feng Ma, Wen Ma, Peng Zang, Ying Chen
Ping Zhang, Ying Zhu, Tong Zhou, Graduate School, Hebei North University, Zhangjiakou 075000, Hebei Province, China
Pu Chen, Peng Zang, Key Laboratory of Aerospace Nutrition and Food Engineering, China Astronaut Research and Training Center, Beijing 100094, China
Zhe-Yi Han, Jian-Feng Ma, Wen Ma, Ying Chen, Department of Gastroenterology, The Air Force Medical Center, Beijing 100142, China
Jun Xiao, Department of Blood Transfusion, Air Force Medical Center, Beijing 100142, China
Co-first authors: Ping Zhang and Ying Zhu.
Co-corresponding authors: Peng Zang and Ying Chen.
Author contributions: Zhang P drafted the manuscript and conducted experiments on animal feeding, establishment of animal models, sampling, Western blotting, RT-qPCR, 16SrRNA sequencing, etc.; Zhu Y assisted in animal sampling, model building, and 16SrRNA experiments; Chen P and Han ZY assisted in the methodology and validation of this study; Zhou T, Ma JF and Ma W participated in the supervision of the writing of this paper; Xiao J assisted in the data statistics and verification of this study; Both Zang P and Chen Y have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Zang P designed and supervised the whole process of the project. He provided guidance on the simulated microgravity model. Chen Y supervised the experiments, reanalysis and interpretation of the data, drew graphs, revised the manuscript, and provided feedback on the complete manuscript. The cooperation between Zang P and Chen Y was essential for the publication of this manuscript.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (Approval Number: ACC-IACUC-2021-014).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data is available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ying Chen, PhD, Associate Professor, Deputy Director, Occupational Physician, Department of Gastroenterology, The Air Force Medical Center, No. 30 Fucheng Road, Haidian District, Beijing 100142, China. cy20020910@163.com
Received: April 29, 2024
Revised: September 5, 2024
Accepted: October 12, 2024
Published online: January 7, 2025
Processing time: 224 Days and 3.6 Hours
Abstract
BACKGROUND

Simulated microgravity environment can lead to gastrointestinal motility disturbance. The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor (SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells. Moreover, intestinal flora can also affect the regulation of SCF/c-kit signaling pathway, thus affecting the expression of Cajal stromal cells. Cajal cells are the pacemakers of gastrointestinal motility.

AIM

To investigate the effects of Bifidobacterium lactis (B. lactis) BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.

METHODS

The internationally recognized tail suspension animal model was used to simulate the microgravity environment, and 30 rats were randomly divided into control group, tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days. The tail group was given B. lactis BLa80 by intragastric administration, and the other two groups were given water intragastric administration, the concentration of intragastric administration was 0.1 g/mL, and each rat was 1 mL/day. Hematoxylin & eosin staining was used to observe the histopathological changes in each segment of the intestine of each group, and the expression levels of SCF, c-kit, extracellular signal-regulated kinase (ERK) and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR. The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.

RESULTS

Simulated microgravity resulted in severe exfoliation of villi of duodenum, jejunum and ileum in rats, marked damage, increased space between villi, loose arrangement, shortened columnar epithelium of colon, less folds, narrower mucosal thickness, reduced goblet cell number and crypts, and significant improvement after probiotic intervention. Simulated microgravity reduced the expressions of SCF and c-kit, and increased the expressions of ERK and P-ERK in the gastric antrum of rats. However, after probiotic intervention, the expressions of SCF and c-kit were increased, while the expressions of ERK and P-ERK were decreased, with statistical significance (P < 0.05). In addition, simulated microgravity can reduce the operational taxonomic unit (OTU) of the overall intestinal flora of rats, B. lactis BLa80 can increase the OTU of rats, simulated microgravity can reduce the overall richness and diversity of stool flora of rats, increase the abundance of firmicutes in stool flora of rats, and reduce the abundance of Bacteroides in stool flora of rats, most of which are mainly beneficial bacteria. Simulated microgravity can increase the overall richness and diversity of mucosal flora, increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora, and decrease the abundance of firmicutes, most of which are proteobacteria. After probiotics intervention, the overall Bacteroidetes trend in simulated microgravity rats was increased.

CONCLUSION

B. lactis BLa80 can ameliorate intestinal mucosal injury, regulate intestinal flora, inhibit ERK expression, and activate the SCF/c-kit signaling pathway, which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.

Keywords: Simulated microgravity; Rat; Intestinal flora; Gastrointestinal motility; Stem cell factor/c-kit signaling pathway

Core Tip: Previous studies have found that the simulated microgravity environment can cause gastrointestinal motility disorders in rats, but the mechanism is not clear. Considering that changes in intestinal mechanical barrier and biological barrier as well as stem cell factor (SCF)/c-kit signaling pathway related to Cajal stromal cells are closely related to gastrointestinal motility, we used protein molecular biology tests and bioinformatics methods to identify the effects and mechanisms of simulated microgravity environment on gastrointestinal motility in rats. And the effect of Bifidobacterium lactis (B. lactis) BLa80 after intervention. This study demonstrated for the first time that B. lactis BLa80 may affect the changes of gastrointestinal motility by improving intestinal mucosal barrier, improving intestinal flora dysregulation, and up-regulating SCF/c-kit signaling pathway.