Dendrobium officinale alleviates high-fat diet-induced nonalcoholic steatohepatitis by modulating gut microbiota

Abstract

IntroductionThe gut microbiota plays an important role in the development of nonalcoholic steatohepatitis (NASH). This study investigated the preventive effect of Dendrobium officinale (DO), including whether its effect was related to the gut microbiota, intestinal permeability and liver inflammation.MethodsA NASH model was established in rats using a high-fat diet (HFD) and gavage with different doses of DO or Atorvastatin Calcium (AT) for 10 weeks. Body weight and body mass index along with liver appearance, weight, index, pathology, and biochemistry were measured to assess the preventive effects of DO on NASH rats. Changes in the gut microbiota were analyzed by 16S rRNA sequencing, and intestinal permeability and liver inflammation were determined to explore the mechanism by which DO treatment prevented NASH.ResultsPathological and biochemical indexes showed that DO was able to protect rats against HFD-induced hepatic steatosis and inflammation. Results of 16S rRNA sequencing showed that Proteobacteria, Romboutsia, Turicibacter, Lachnoclostridium, Blautia, Ruminococcus_torques_group, Sutterella, Escherichia-Shigella, Prevotella, Alistipes, and Lactobacillus_acidophilus differed significantly at the phylum, genus, and species levels. DO treatment modulated the diversity, richness, and evenness of gut microbiota, downregulated the abundance of the Gram-negative bacteria Proteobacteria, Sutterella, and Escherichia-Shigella, and reduced gut-derived lipopolysaccharide (LPS) levels. DO also restored expression of the tight junction proteins, zona occludens-1 (ZO-1), claudin-1, and occludin in the intestine and ameliorated the increased intestinal permeability caused by HFD, gut microbiota such as Turicibacter, Ruminococcus, Escherichia-Shigella, and Sutterella, and LPS. Lower intestinal permeability reduced LPS delivery to the liver, thus inhibiting TLR4 expression and nuclear factor-kappaB (NF-κB) nuclear translocation, improving liver inflammation.DiscussionThese results suggest that DO may alleviate NASH by regulating the gut microbiota, intestinal permeability, and liver inflammation.

Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…Therefore, LPS binds to LPS-binding proteins and then binds to TLR-4, triggering insulin resistance, followed by an immune response and greater propensity for inflammation; that is, LPS increases the levels of gut-derived TLR4 since this receptor is activated in hepatic Kupffer cells and stellate cells. Further pro-inflammatory and pro-fibrotic pathways are stimulated through several cytokines, including IL1, IL6, and TNF [77,[131][132][133][134]. In MAFLD, TLR-4 signaling initiates local inflammatory changes and develops hepatic steatosis.…”

“…Clinical studies demonstrated that serum or visceral adipose omentin levels were significantly reduced in subjects with DM2, metabolic syndrome, obesity, and NAFLD. For these reasons, omentin could be used as a non-invasive diagnostic biomarker for MAFLD [133,153,154].…”

The Gut Microbiome in Aging and Ovarian Cancer

“…Similar results were documented in another report in which mice receiving cisplatin, Tripterygium glycosides, and oral antibiotics had greater subcutaneous ovarian tumor growth than mice given the same treatment without antibiotics. FMT from tumor‐naïve donor mice reduced tumor growth in the antibiotic‐treated mice to levels comparable to those not given antibiotics [23]. Because both the retrospective human study and these murine studies indicate negative effects of antibiotics on ovarian cancer metastasis and treatment, it will be important to further validate this research and carefully weigh the benefits and detriments of antibiotic use in ovarian cancer patients, especially during treatment.…”

“…Traditional Chinese medicines have been shown to modulate the gut microbiome and reduce tumor burden in rodent models of ovarian cancer. However, the changes seen in the gut microbiome in each study do not overlap well between studies, do not line up well with changes seen in human ovarian cancer patients compared to control subjects, and do not result in the experimentally treated animals having a gut microbiome that better resembles their respective tumor‐naïve controls [23, 34, 103]. The lack of similarity in gut microbiome changes between experiments is reasonable considering that each study was testing a different compound.…”

“…The current evidence for causal relationships between gut microbiome changes and ovarian cancer symptoms is limited to the two studies in which treatment of ovarian cancer‐bearing mice with FMT from ovarian cancer patients promoted tumor growth via IFN‐γ and CD8 + T cell or Hedgehog and TNF‐α/IL‐1β pathways [16, 17]. Research on the benefits of gut microbiome remediation in ovarian cancer treatment is limited to a few studies in which mice have benefitted from FMT from healthy donors or their own stool banked prior to chemotherapy [16, 17, 25], or pilot studies showing gut microbiome modulation via Traditional Chinese Medicine [23, 34, 103]. Importantly, to our knowledge, there are no clinical trials on gut microbiome remediation to enhance ovarian cancer treatment.…”