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Updated: Jan 10, 2026
An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota
Published on: July 31, 2019
Interindividual variability in gut microbiome mediates the efficacy of resistant starch on MASLD
Xiaoxue Long1, Hui Wang2, Yuwei Lu1
1State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Our randomized, placebo-controlled trial showed resistant starch (RS), a type of prebiotic, has therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we observed its heterogeneous efficacy, where 30% of participants exhibited limited benefits, which was replicated in a multi-center trial (ChiCTR2300074588). Multi-omics analysis and fecal microbiota transplantation identified baseline microbiota as a dominant contributor of response. Further population stratification and network analysis combined with in vitro and in vivo experiments revealed Prevotella as the key cause of low response by inhibiting RS-degrading bacteria, thereby impairing RS utilization. Conversely, Bifidobacterium pseudocatenulatum RRP01, a strain isolated from our cohort, restored RS degradation and improved Prevotella-attenuated RS response. Furthermore, we developed a predictive model integrating baseline microbial and clinical features (area under the curve [AUC] = 0.74-0.87), enabling stratification for personalized interventions. Our study indicates that gut microbiota determines the heterogeneity in RS efficacy and offers possibilities for novel microbiota-oriented precision therapeutics for MASLD.
Insights
Resistant starch (RS) shows benefits for metabolic dysfunction-associated steatotic liver disease (MASLD), but gut bacteria influence its effectiveness. Specific bacteria like Prevotella reduce benefits, while Bifidobacterium can restore them, enabling personalized MASLD treatments.
Area of Science:
- Gastroenterology and Hepatology
- Microbiome Research
- Metabolic Diseases
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern.
- Prebiotics, such as resistant starch (RS), have shown potential therapeutic effects.
- Individual responses to RS interventions for MASLD are variable.
Purpose of the Study:
- To investigate the heterogeneous efficacy of resistant starch (RS) in patients with MASLD.
- To identify the role of gut microbiota in modulating RS response.
- To develop a predictive model for personalized MASLD treatment strategies.
Main Methods:
- Randomized, placebo-controlled trial and a multi-center trial.
- Multi-omics analysis and fecal microbiota transplantation (FMT).
- In vitro and in vivo experiments, population stratification, and network analysis.
Main Results:
- Approximately 30% of participants showed limited benefits from RS, consistent across trials.
- Baseline gut microbiota composition significantly impacts RS efficacy.
- Prevotella species were identified as key inhibitors of RS utilization, while Bifidobacterium pseudocatenulatum RRP01 restored RS degradation.
- A predictive model integrating microbial and clinical data achieved an AUC of 0.74-0.87.
Conclusions:
- Gut microbiota composition is a primary determinant of variable RS efficacy in MASLD.
- Targeting specific microbial pathways offers a novel approach for precision therapeutics in MASLD.
- Personalized interventions based on microbial profiles can optimize RS treatment outcomes.
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