Molecular Characterization of the Fecal Microbiota in Patients with Nonalcoholic Steatohepatitis – A Longitudinal Study

Abstract

BackgroundThe human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied.MethodsFecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG).ResultsA total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P = 0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R2 = 0.4820, P = 0.0028) and increase in Bacteroidetes (R2 = 0.4366, P = 0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.ConclusionsNASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.

Gut microbiome and nonalcoholic fatty liver diseases

“…Initial evidence for an altered gut microbiota in obesity is the observation by Ley et al that ob/ob mice (9) and obese patients (10) exhibit reduced abundance of Bacteroidetes and proportionally increased abundance of Firmicutes. Altered gut microbiota in obesity was also observed by other researchers, although the observed changes were usually different (11)(12)(13)(14)(15)(16)(17)(18), and frequently opposite (12)(13)(14)(15)(16)(17)(18) to the observations of Ley et al Note that only three studies stated that the enrolled patients and controls did not take antibiotics in the 3-mo period before sample collection; and all three studies reported an increased Bacteroidetes/Firmicutes ratio in the gut of obese patients (12)(13)(14)19) (Table 1). Our group paid particular attention to proton pump inhibitors and histamine receptor antagonists (14,19) as these agents are known to affect Firmicutes (20).…”

“…In another randomized controlled trial examining the effects of probiotic therapy on NASH patients using Lactobacillus and Bifidobacterium spp. no significant difference in BMI, fasting glucose, cholesterol, or triglyceride was observed between the probiotics treated group and the control (18).…”

Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet

“…Indeed, a few studies have examined dysbiosis in NAFLD ( Table 1). Patients with NASH harbor a lower abundance of Faecalibacterium and Firmicutes (Clostridiales family, Anaerosporobacter) but a higher abundance of Parabacteroides and Allisonella in their fecal microbiome (45). Importantly, it has been reported that improved intrahepatic TG content is related to a lower abundance of Firmicutes and a higher abundance of Bacteroidetes (45) (15).…”

“…Patients with NASH harbor a lower abundance of Faecalibacterium and Firmicutes (Clostridiales family, Anaerosporobacter) but a higher abundance of Parabacteroides and Allisonella in their fecal microbiome (45). Importantly, it has been reported that improved intrahepatic TG content is related to a lower abundance of Firmicutes and a higher abundance of Bacteroidetes (45) (15). In support of these studies, pediatric patients with NAFLD showed an increase in Bradyrhizobium, Anaerococcus, Peptoniphilus, Propionibacterium acnes, Dorea, and Ruminococcus and a decrease in Oscillospira and Rikenellaceae (44).…”

Bacterial Infections of the Ear, Nose and Throat: A Delicate Treatment

“…Faecalibacterium prausnitzii также считается противовоспа-лительным компонентом микрофлоры, умень шение ее представленности ассоциировано с риском развития мета-болических нарушений и воспалительных заболеваний кишечника [14]. У пациентов с метаболическим синдро-мом, сахарным диабетом 2-го типа, ожирением доля Faecalibacterium prausnitzii достоверно снижается [15][16][17][18].…”