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Zhao et al. Microbiome Res Rep. 2025;4:28  https://dx.doi.org/10.20517/mrr.2025.12  Page 5 of 13

               Table 2. Changes in BSH expression or activity across different stages of MASLD
                                                                      BSH activity   Microbiome
                BSH            Ethnicity/animal
                change a Subjects  model     Intervention Group       evaluation   sequencing    References
                                                                      method
                                                                                   method
                Metabolic dysfunction-associated steatotic liver disease (MASLD)
                ↓      Adults  American      /         mild MASLD (72) vs.   BSH gene   Metagenomics  [9,59,60]
                                                       Control (308)  abundance
                ↓      Children  Asian       /         MASLD (32) vs. HC   Microbial relative   Metagenomics  [25]
                                                       (36)           abundance,
                                                                      KEGG analysis
                ↑      Adults  American      /         MASLD (57) vs. HC   Microbial relative   16s rRNA  [11]
                                                       (18)           abundance
                ↓      Mice   C57BL/6J       /         HFD (6) vs. Chow (9)  Microbial relative   16s rRNA  [22]
                                                                      abundance
                ↓      Mice   C57BL/6J       Drug      HFD + IsA (6) vs.   In vitro assay  16s rRNA  [28]
                                                       Chow vs. HFD (6)
                ↓      Mice   C57BL/6J       Drug      HFD (8) vs. CN (8)  Microbial relative   16s rRNA  [29]
                                                                      abundance
                ↓      Mice   C57BL/6J       Drug      ZKY (6) vs. HFD (6)   BSH gene copy   16s rRNA  [26]
                                                       vs. Con (6     number
                ↑      Rats   Wistar         BSH inhibitor  AAA-10 (8) vs.   In vitro assay  /   [31]
                                                       Vehicle (8)
                ↑      Mice   C57BL/6J       BSH inhibitor  CAPE (5) vs. Vehicle   In vitro assay  16s rRNA  [17]
                                                       (5)
                ↑      Mice   C57BL/6J       Drug      PCPE (8) vs. HFD (8)  In vitro assay  16s rRNA  [30]
                Metabolic-Associated Steatohepatitis (MASH)
                ↓      Mice   C57BL/6J       Probiotics  ALDH2-/--MCD (5)   In vitro assay  16s rRNA  [32]
                                                       vs. WT-MCD (5)
                ↓      Mice   C57BL/6J       Drug      OCA (8) vs. Vehicle   In vitro assay  16s rRNA  [34]
                                                       (8)
                ↑      Mice   C57BL/6J       /         HFHC (8) vs. HF (8)   Microbial relative   16s rRNA  [33]
                                                       vs. Con (8)    abundance
                Advanced liver diseases (Fibrosis and cirrhosis)
                ↓      Adults  Asian      /            Hepatic fibrosis (17)   Microbial relative   16s rRNA  [18]
                                                       vs. HC (10)    abundance,
                                                                      bile acid profile
                                                                      analysis
                ↓      Adults  American   /            Advanced MASLD   BSH gene   Metagenomics  [9,59,60]
                                                       (Fibrosis,14) vs.   abundance
                                                       Control (308)
                ↓      Adults  Asian      /            Liver cirrhosis (114) vs.  BSH gene   Metagenomics  [9,38]
                                                       Control (123)  abundance
                ↓      Mice   C57BL/6J    Probiotics   TAA (6) vs. Control   Bile acids profile   16s rRNA  [18]
                                                       (6)            analysis
                ↓      Mice   C57BL/6J    /            Tlr4-/- (8) vs. WT   Microbial relative   16s rRNA  [36]
                                                       (10)           abundance
                ↓      Mice   C57BL/6J    Drug         DDC + KH (5) vs.   Microbial relative   16s rRNA  [35]
                                                       DDC+H2O (5)    abundance
                ↓      Mice   C57BL/6J    Drug         DDC (5) vs. Control   In vitro assay  16s rRNA  [19]
                                                       (5)
                ↓      Mice   C57BL/6J    Probiotics   BDL + LGG (7) vs. BDL  In vitro assay  /  [37]
                                                       (7)
               a
                ↑, gut BSH activity was higher in the disease state or before intervention; ↓, gut BSH activity was lower in the disease state or before intervention.
               The numbers in the “Group” column indicate the total number of participants or animals per group. BSH: Bile salt hydrolase; KEGG: kyoto
               encyclopedia of genes and genomes; IsA: ilexsaponin A1; LGG: Lactobacillus rhamnosus GG; HC: health control; HFD: high-fat diet; CN: control;
               CAPE: caffeic acid phenethyl ester; PCPE: Penthorum chinense Pursh. extract; ALDH2-/--MCD & WT-MCD: ALDH2 knockout mice and wild-type
               littermate mice were fed a methionine-and choline-deficient diet; OCA: obeticholic acid; HFHC: high-fat and high-cholesterol diet; HF: high fat
               diet; TAA: thioacetamide; DDC: 3,5-diethoxycarbonyl-1,4-dihydrocollidine; KH: Kuhuang treatment; BDL: bile duct ligation; AAA-10:
               small-molecule inhibitor of gut bacterial BSHs.
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