Page 15 - Read Online

Page 10 of 13 Zhao et al. Microbiome Res Rep. 2025;4:28 https://dx.doi.org/10.20517/mrr.2025.12

Therapeutic implications and potential interventions targeting BSH
Studying the role of microbial BSH in host metabolism presents methodological challenges due to the
variability in gut microbiota composition and the complexity of BA metabolism. Longitudinal studies are
therefore necessary to understand the long-term effects of microbial BSH on MASLD progression and to
identify reliable biomarkers for disease monitoring. In addition, personalized approaches that account for
individual differences in gut microbiota and metabolic responses will be critical for the development of
effective BSH-targeted therapies.

Recent advances in microbiome research, metagenomics, and metabolomics are opening new avenues for
understanding the role of BSH in MASLD and for developing targeted interventions. BSH not only supports
bacterial colonization and survival in the gastrointestinal tract but also significantly affects host glucose and
lipid metabolism and the regulation of inflammation. Its regulatory effects are mediated through BAs,
especially via alterations in the composition and spatial distribution of secondary BAs, which interact with
specific receptors and the NLRP3 inflammasome. These interactions indirectly influence the synthesis and
secretion of key metabolic regulators such as cholesterol, ceramides, and GLP-1, contributing to the
restoration of metabolic balance. This highlights the potential of BSH as a therapeutic target for MASLD.
Consequently, the use of probiotics or natural small-molecule compounds to modulate microbial BSH gene
expression or enzyme activity has become a focal point of research aimed at improving MASLD-related
metabolic disorders .
[28]

Although extensive studies have explored the structure, function, and substrate specificity of various BSH
enzymes, much remains to be discovered about gut bacteria and their functions . With ongoing
[58]
advancements in sequencing technologies, additional BSH variants are expected to be identified.
Understanding the enzymatic properties of these variants will be crucial for developing personalized
probiotics and more effective diagnostic and therapeutic tools.

CONCLUSION
Gut microbial BSH activity tends to decline during the development and progression of MASLD due to
factors such as changes in gut microbiota composition, host metabolic status, inflammation, and dietary
influences. BSH plays a critical role in maintaining BA metabolic balance and significantly impacts the
progression and management of MASLD. A deeper understanding of the intricate relationship between gut
microbiota, BSH, and MASLD will provide valuable insights for the development of targeted therapeutic
strategies. Further research is needed to clarify the mechanisms by which BSH changes influence liver health
and to devise effective interventions for MASLD. Targeting BSH represents a promising approach for
modulating BA metabolism and improving metabolic health, highlighting the crucial role of the gut
microbiota in disease management.

DECLARATIONS
Acknowledgments
Graphic elements used in the figures were obtained from BioGDP (https://www.biogdp.com) and assembled
by the authors.

Authors’ contributions
Drafted and revised the manuscript: Zhao W, Ni Y, Wang H, Zheng M
Conceived and designed this project: Ni Y