Dataset Information

Nutrition and Genetics in NAFLD: The Perfect Binomium.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) represents a global healthcare burden since it is epidemiologically related to obesity, type 2 diabetes (T2D) and Metabolic Syndrome (MetS). It embraces a wide spectrum of hepatic injuries, which include simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The susceptibility to develop NAFLD is highly variable and it is influenced by several cues including environmental (i.e., dietary habits and physical activity) and inherited (i.e., genetic/epigenetic) risk factors. Nonetheless, even intestinal microbiota and its by-products play a crucial role in NAFLD pathophysiology. The interaction of dietary exposure with the genome is referred to as 'nutritional genomics,' which encompasses both 'nutrigenetics' and 'nutriepigenomics.' It is focused on revealing the biological mechanisms that entail both the acute and persistent genome-nutrient interactions that influence health and it may represent a promising field of study to improve both clinical and health nutrition practices. Thus, the premise of this review is to discuss the relevance of personalized nutritional advices as a novel therapeutic approach in NAFLD tailored management.

SUBMITTER: Meroni M

PROVIDER: S-EPMC7215858 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Nutrition and Genetics in NAFLD: The Perfect Binomium.

Meroni Marica M Longo Miriam M Rustichelli Alice A Dongiovanni Paola P

International journal of molecular sciences 20200423 8

Nonalcoholic fatty liver disease (NAFLD) represents a global healthcare burden since it is epidemiologically related to obesity, type 2 diabetes (T2D) and Metabolic Syndrome (MetS). It embraces a wide spectrum of hepatic injuries, which include simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The susceptibility to develop NAFLD is highly variable and it is influenced by several cues including environmental (i.e., dietary habits and ph ...[more]

PMID: 32340286

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Project description:BackgroundHuman body microbiotas are influenced by several factors, including the interaction of the host with the environment and dietary preferences. The role of host genetics in modulating the liver microbiota in the context of NAFLD remains unknown. To address this gap, we examined the interplay between the liver metataxonomic profile and host genetics.MethodsWe obtained 16S rRNA gene sequences from liver biopsies and genotypes by Taqman-assays in 116 individuals. We compared taxon abundance at the genus level across host genotypes using dominant models of inheritance. We focused the analysis on variants influencing the risk/ protection against NAFLD-histological severity (PNPLA3-rs738409, TM6SF2-rs58542926, MBOAT7-rs641738, and HSD17B13-rs72613567) and a variant influencing macronutrient intake (FGF21-rs838133). We also explored the variants' combined effect via a polygenic risk score (PRS).FindingsWe identified at least 18 bacterial taxa associated with variants in the selected loci. Members of the Gammaproteobacteria class were significantly enriched in carriers of the rs738409 and rs58542926 risk-alleles, including Enterobacter (fold change [FC]=6.2) and Pseudoalteromonas (FC=2) genera, respectively. Lawsonella (1.6-FC), Prevotella_9 (FC=1.5), and Staphylococcus (FC=1.3) genera were enriched in rs838133-minor allele carriers, which is linked to sugar consumption and carbohydrate intake. Tyzzerella abundance (FC=2.64) exhibited the strongest association (p = 0.0019) with high PRS values (>4 risk alleles). The percentage of genus-level taxa variation explained by the PRS was ∼7.4%, independently of liver steatosis score and obesity.InterpretationWe provided evidence that genetic variation may influence the liver microbial DNA composition. These observations may represent potentially actionable mechanisms of disease.FundingThis study was partially supported by grants PICT 2018-889, PICT 2019-0528, PICT2016-0135 and PICT 2018-0620 (Agencia Nacional de Promoción Científica y Tecnológica, FONCyT), CONICET Proyectos Unidades Ejecutoras 2017, PUE 0055.

Project description:Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment.

Dataset Information

Nutrition and Genetics in NAFLD: The Perfect Binomium.

Publications

Nutrition and Genetics in NAFLD: The Perfect Binomium.

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