Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study

Feb 28, 2018Nutrition, metabolism, and cardiovascular diseases : NMCD

Gut bacteria types linked to liver damage in lean NASH patients regardless of calorie intake

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Abstract

Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007).

NASH patients displayed differences in the abundance of gut bacteria, specifically Faecalibacterium, Ruminococcus, Lactobacillus, and Bifidobacterium, compared to controls.
Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004) than obese counterparts.
Obese NASH patients exhibited an enrichment of Lactobacilli (p = 0.002).
Overweight NASH patients showed reduced levels of Bifidobacterium (p = 0.018).
Lean NASH patients had a deficiency in Lactobacillus compared to overweight and obese NASH patients.
Qualitative differences in the gut microbiome between lean NASH and overweight/obese NASH were noted but not statistically significant (p = 0.618).

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BACKGROUND AND AIM: The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences.

METHODS AND RESULTS: We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota.

CONCLUSION: Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits.

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Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study

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