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Treatment of nonalcoholic steatohepatitis with probiotics
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Treatment of nonalcoholic steatohepatitis with probiotics

Background and aims: Gut microbiota is involved in energy harvesting and systemic inflammation. Probiotics ameliorate nonalcoholic steatohepatitis (NASH) in animal studies. We aimed to test the efficacy of probiotics treatment and study the gut microbiota composition of humans with NASH.

Methods: Patients with biopsy-confirmed NASH were randomized to receive probiotics (including 4 Lactobacillus strains and Bifidobacterium bifidum; 10 subjects) or usual care (10 subjects) for 6 months. The primary endpoint was change in hepatic triglyceride content as measured by proton-magnetic resonance spectroscopy. Gut microbiota of NASH subjects was compared to control subjects matched for age, gender and body mass index, and was assessed serially during treatment. Analysis was performed by pyrosequencing of 16S rRNA genes from fresh morning stool samples (454 Life Sciences, Branford, CT).

Results: Hepatic triglyceride content decreased by a median of 7.6% (IQR -11.5%, -0.2%) in the probiotics group (P=0.028) and increased by 0.9% (IQR -4.2%, 2.4%) in the usual care group (P=0.80). The probiotics group tended to have greater reductions in serum alanine aminotransferase (-20 IU/l vs. 10 IU/l; P=0.44), aspartate aminotransferase (-7 IU/l vs. 11 IU/l; P=0.11) and gamma-glutamyl transpeptidase (-6 IU/l vs. 14 IU/l; P=0.28) than the usual care group. The change in body mass index and other metabolic parameters did not differ between the two groups. Analysis of 8 NASH subjects and 6 controls yielded 1,287,850 partial bacterial 16S rRNA sequences. Compared to controls, NASH subjects had higher relative abundance of Bacteroides (87.8% vs. 80.8%), but lower abundance of Firmicutes (10.3% vs. 13.5%) and Fusobacterium (0.27% vs. 3.9%) (all P<10-6). Probiotics reduced the abundance of Bacteroides (92.1% to 89.1%; P<10-6) and increased the abundance of Firmicutes (6.6% to 9.4%; P<10-6), but the change was not observed in the usual care group.

Conclusions: Probiotics treatment reduces hepatic triglyceride content in patients with NASH. Altered gut microbiota is associated with NASH, and may be modified by probiotics. Our results support further evaluation of probiotics as a treatment for NASH in larger clinical trials. (ClinicalTrials.gov number, NCT00870012)
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