Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations
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Study information
incomplete
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Ni Y., Qian L., Siliceo S.L., Long X., Nychas E., Liu Y., Ismaiah M.J., Leung H., Zhang L., Gao Q., Wu Q., Zhang Y., Jia X., Liu S., Yuan R., Zhou L., Wang X., Li Q., Zhao Y., El-Nezami H., Xu A., Xu G., Li H., Panagiotou G., Jia W.
Journal
Cell metabolism
Year
2023
Keywords:
BCAAs, Bacteroides stercoris, gut microbiota, intrahepatic triglyceride content, lipopolysaccharides, microbiota transplantation, microbiota-directed foods, non-alcoholic fatty liver disease, resistant starch
Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic dysfunction for which effective interventions are lacking. To investigate the effects of resistant starch (RS) as a microbiota-directed dietary supplement for NAFLD treatment, we coupled a 4-month randomized placebo-controlled clinical trial in individuals with NAFLD (ChiCTR-IOR-15007519) with metagenomics and metabolomics analysis. Relative to the control (n = 97), the RS intervention (n = 99) resulted in a 9.08% absolute reduction of intrahepatic triglyceride content (IHTC), which was 5.89% after adjusting for weight loss. Serum branched-chain amino acids (BCAAs) and gut microbial species, in particular Bacteroides stercoris, significantly correlated with IHTC and liver enzymes and were reduced by RS. Multi-omics integrative analyses revealed the interplay among gut microbiota changes, BCAA availability, and hepatic steatosis, with causality supported by fecal microbiota transplantation and monocolonization in mice. Thus, RS dietary supplementation might be a strategy for managing NAFLD by altering gut microbiota composition and functionality.
Experiment 1
incomplete
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Right lobe of liver 2nd lobe,Gall bladder lobe,Liver right lobe,Lobus hepaticus dexter,Lobus hepatis dexter,Right hepatic lobe,Right liver lobe,Second lobe,Right lobe of liver,right lobe of liver
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Non-alcoholic fatty liver disease fatty liver disease, nonalcoholic,fatty liver disease, nonalcoholic, susceptibility to, 1,liver disease, alcoholic, susceptibility to, 1,NAFLD - Nonalcoholic Fatty Liver Disease,NAFLD - nonalcoholic fatty liver disease,NAFLD1,non-alcoholic fatty liver,non-alcoholic fatty liver disease,Nonalcoholic Fatty Liver Disease,nonalcoholic fatty liver disease,Non-alcoholic fatty liver disease
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control Starch
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Resistant Starch
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- high-amylose maize resistant starch type 2 (HAM-RS2) 40 g/day (delivered as food product) for 4 months (120 days)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 97
- Group 1 sample size Number of subjects in the case (exposed) group
- 99
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Participants using antibiotics, probiotics, or prebiotics within 3 months before enrollment were excluded.
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- PERMANOVA
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- body mass index, waist circumference, Confounders controlled for: "FAT" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.FAT
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- unchanged
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Experiment 2
incomplete
Differences from previous experiment shown
Subjects
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Liver Iecur,Jecur,Liver,liver
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Non-alcoholic fatty liver disease , Response to high fat food intake fatty liver disease, nonalcoholic,fatty liver disease, nonalcoholic, susceptibility to, 1,liver disease, alcoholic, susceptibility to, 1,NAFLD - Nonalcoholic Fatty Liver Disease,NAFLD - nonalcoholic fatty liver disease,NAFLD1,non-alcoholic fatty liver,non-alcoholic fatty liver disease,Nonalcoholic Fatty Liver Disease,nonalcoholic fatty liver disease,Non-alcoholic fatty liver disease,Response to high fat food intake,response to high fat food intake
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CS-FMT
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- RS-FMT
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Fecal slurry from human RS donors (whose IHTC reduction matched group mean) transplanted into antibiotic-treated mice
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- -NA-
Lab analysis
Statistical Analysis
- Statistical test
- PERMANOVA
- Spearman Correlation
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
Experiment 3
incomplete
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Liver , Colon Iecur,Jecur,Liver,liver,Hindgut,Large bowel,Posterior intestine,Colon,colon
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HFHC + PBS
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HFHC + B. stercoris
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Daily oral gavage of 5 × 10⁹ CFU live B. stercoris for 8 weeks
- Group 1 sample size Number of subjects in the case (exposed) group
- 16
Lab analysis
- Sequencing type
- PCR
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Statistical test
- Kruskall-Wallis
- ANOVA
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
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