Excessive consumption of the simple sugar fructose, which induces excessive hepatic lipogenesis and gut dysbiosis, is a risk factor for cardiometabolic diseases. Here we show in male mice that the gut microbiome, when adapted to dietary fibre inulin, catabolizes dietary fructose and mitigates or reverses insulin resistance, hepatic steatosis and fibrosis. Specifically, inulin supplementation, without affecting the host’s small intestinal fructose catabolism, promotes the small intestinal microbiome to break down incoming fructose, thereby decreasing hepatic lipogenesis and fructose spillover to the colonic microbiome. Inulin also activates hepatic de novo serine synthesis and cystine uptake, augmenting glutathione production and protecting the liver from fructose-induced lipid peroxidation. These multi-modal effects of inulin are transmittable by the gut microbiome, where Bacteroides acidifaciens acts as a key player. Thus, the gut microbiome, adapted to use inulin (a fructose polymer), efficiently catabolizes dietary monomeric fructose, thereby protecting the host. These findings provide a mechanism for how fibre can facilitate the gut microbiome to mitigate the host’s exposure to harmful nutrients and disease progression.
Experiment 1
Subjects
- Location of subjects
- United States of America
- 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
- Diabetes mellitus Diabetes,diabetes,diabetes mellitus,diabetes mellitus (disease),Diabetes mellitus (disorder),Diabetes mellitus, NOS,Diabetes NOS,DM,DM - Diabetes mellitus,Diabetes mellitus
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control or unexposed
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Case or exposed
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Mice received insulin supplemented diet with or without HFCS in drinking water
- Group 0 sample size Number of subjects in the control (unexposed) group
- 3
- Group 1 sample size Number of subjects in the case (exposed) group
- 3
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 1 week
Lab analysis
- Sequencing type
- 16S
- 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
- RT-qPCR
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- ANOVA
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.005
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 0.05
- Matched on Factors on which subjects have been matched on in a case-control study
- sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "medication status" 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.medication status
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Experiment 2
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Experiment 3
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
Experiment 4
Differences from previous experiment shown
Subjects
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Rattus norvegicus
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- unchanged
