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. 2022 Jul 28;28(28):3555–3572. doi: 10.3748/wjg.v28.i28.3555

Table 2.

Gut microbiota-related treatment toward hepatitis B virus-related fibrosis and complications (studies in animal models)

Ref.
Study populations (n)
Treatment and grouping (n)
Conclusions
Antiviral therapy
Li et al[96] AAV-mediated persistent HBV infection (AAV-HBV) mice (n = 10) 35 d after HBV infection, 4 wk of daily ETV treatment. ETV (n = 5) Gut microbiota dysbiosis of the AAV-HBV mice was reversed by ETV treatment with restored α diversity and changed proportion of Akkermansia, Lacnospiracea and Marvinbryantia
Rifaximin
Kang et al[105] Germ-free mice (n = 16) 15 d of rifaximin 100 mg/(kg·d), or humanized with stools from a HCV-induced cirrhotic patient with MHE. Rifaximin (n = 4); Humanized (n = 4); Rifaximin + humanized (n = 4) Rifaximin beneficially altered intestinal ammonia generation by regulating intestinal glutaminase expression independent of gut microbiota. MHE-associated fecal colonization resulted in intestinal and systemic inflammation. It was ameliorated with rifaximin
Engineered probiotics
Nicaise et al[120] Ornithine transcarbamoylase-deficient Sparse-fur mice; Carbon tetrachloride rats; Thioacetamide-induced acute liver failure mice NCIMB8826 (wild-type strain Lactobacillus plantarum), or EV101 (engineered Lactobacillus plantarum, LDH-/AlaD+) oral and intrarectal administration EV101 administration was effective in controlling hyperammonemia in constitutive animal models with a significant effect on survival, which might be involved with direct ammonia consumption in the gut
Kurtz et al[121] Ornithine transcarbamylase-deficient spfash mice; Thioacetamide-induced acute liver failure mice; Healthy volunteers (n = 52) Non-modified Escherichia coli Nissle 1917 (EcN), SYNB1020 (engineered EcN, ΔargR, ΔthyA, malEK:PfnrS-argAfbr) administration SYNB1020 converted NH3 to l-arginine in vitro, and reduced systemic hyperammonemia, improved survival in mouse models. SYNB1020 was well tolerated in healthy volunteers
Ochoa-Sanchez et al[122] Bile-duct ligated rats Non-modified EcN, S-ARG, or S-ARG + BUT administration S-ARG converted ammonia to arginine, it was further modified to additionally synthesize butyrate, which had the potential to prevent HE
FMT
Liu et al[134] Germ-free mice Sterile supernatant or entire stool from pre-FMT and post-FMT cirrhotic patients with HE was transplanted to Germ-free mice Transferred microbiota mediated neuroinflammation. Cirrhosis-associated dysregulation of gut microbiota was related with frontal cortical inflammation

AAV: Adeno-associated virus; HBV: Hepatitis B virus; ETV: Entecavir; HCV: Hepatitis C virus; MHE: Minimal hepatic encephalopathy; HE: Hepatic encephalopathy; FMT: Fecal microbiota transplantation.