Table 2.

Therapeutics in rodent experimental models and patients.

Effect of Antibiotics Treatment in Rodents
Model	Disease	Treatment/Antibiotic	Effect	Reference
Wistar Rats exposed to Ethanol	Alcohol-induced liver injury	Polymixin B and Neomycin	Treatment with antibiotics in rats with alcohol-induced liver injury: ◦reduced the endotoxin levels in plasma ◦reduced aspartate aminotransferase levels ◦reduced the hepatic pathological score ◦prevented hypoxia	[88]
Sprague–Dawley rats exposed to ethanol	Alcohol-induced liver injury	Ampicillin and neomycin	Treatment with antibiotics in rats with alcohol-induced liver injury: ◦inhibited the effect of ethanol ◦reduced the endotoxin levels in plasma	[89]
C57Bl/6 Mice under a High Fat Diet (HFD)	NAFLD	Bacitracin, neomycin and streptomycin (BNS)	Treatment with antibiotics in mice with NAFLD: ◦increased tauro-b-muricholic acid levels ◦inhibited FXR signaling in the ileum ◦reduced hepatic lipid accumulation	[90]
Wistar rats exposed to CCL4	Cirrhosis	Norfloxacin and Vancomycin	Treatment with antibiotics in mice with liver cirrhosis: ◦reduced intestinal mucosa inflammation ◦reduced gut bacterial translocation ◦restored intestinal permeability	[91]
Sprague–Dawley Rats exposed to DEN	HCC	Polymyxin B and Neomycin	Treatment with antibiotics in rats with HCC: ◦reduced the levels of LPS in plasma ◦reduced TNF alpha and IL6 levels ◦reduced liver fibrogenesis and HCC multiplicity ◦reduced levels of cell proliferation in tumor	[83]
C57Bl/6 Mice exposed to DEN/CCL4	HCC	Ampicillin, Vancomycin, Neomycin sulfate and Metronidazole	Treatment with antibiotics in rats with HCC: ◦reduced tumor number, size and liver/body weight ratio ◦reduced expression of cell cycle, fibrosis and inflammatory genes ◦increased liver injury	[81]
C57Bl/6 Mice under a HFD	Obesity-related HCC	Ampicilin, Neomycin, Metronidazole, vancomycin	Treatment with antibiotics in rats with obesity-related HCC: ◦reduced HCC development ◦reduced senescent hematopoietic stem cells	[82]
Effect of Antibiotics Treatment in Patients
Patients	Disease	Treatment/Antibiotic	Effect	Reference
Patients with recurrent hepatic encephalopathy resulting from chronic liver disease	Cirrhosis and Hepatic Encephalopathy	Rifaximin	Treatment with antibiotics in patients with liver cirrhosis: ◦reduced the risk of suffering hepatic encephalopathy ◦reduced the risk of hospitalization associated with hepatic encephalopathy	[92]
Patients with alcohol-related decompensated cirrhosis and ascites	Cirrhosis	Rifaximin	Treatment with antibiotics in patients with liver cirrhosis: ◦reduced the risk complications such as variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis and hepatorenal syndrome ◦increased the five-year probability of survival	[93]
Patients with cirrhosis	Cirrhosis	Rifaximin	Treatment with antibiotics in patients with liver cirrhosis: ◦increased beneficial bacteria Klebsiella	[94]
Patients with cirrhosis	Cirrhosis	Norfloxacin	Treatment with antibiotics in patients with liver cirrhosis: ◦reduced the episodes complications such as spontaneous bacterial peritonitis and hepatorenal syndrome ◦increased the one-year probability of survival	[95]
Effect of Probiotic Administration in Rodents
Model	Disease	Treatment/Probiotic	Effect	Reference
C57Bl/6N Mice exposed to ethanol	Alcoholic Liver Disease (ALD)	L.rhamnosus GG (LGG)	Probiotic administration in mice with alcoholic liver disease: ◦prevented microbiome changes during the disease ◦restored tight junction protein expression ◦reduced endotoxemia and hepatic injury	[96]
C57Bl/6N Mice exposed to ethanol	Alcoholic Liver Disease (ALD)	L.rhamnosus GG (LGG)	Probiotic administration in mice with alcoholic liver disease: ◦reduced hepatic inflammation and liver injury ◦reduced TNF alpha expression ◦inhibited TL 4 and TLR5-mediated endotoxin activation	[97]
Sprague–Dawley rats under a HFD	NAFLD	Lactobacillus paracasei B21060	Probiotic administration in rats with NAFLD: ◦reduced liver inflammation markers ◦reduced cytokines synthesis ◦reduced steatosis ◦preserved gut barrier integrity ◦reduced the relative amount of Enterobacterales and E.coli in colonic mucosa	[98]
C57BL/6J mice exposed to fructose	NAFLD	L.casei Shirota (Lcs)	Probiotic administration in mice with NAFLD: ◦reduced steatosis ◦reduced alanine-aminotransferase (ALT) levels ◦reduced the activation of TL 4	[99]
C57BL6/N mice with subcutaneous tumor injection	HCC	L.rhamnosus GG (LGG), viable E.coli Nissle 1917 (EcN), and heat-inactivated VSL#3 (1:1:1)	Probiotic administration in mice with HCC: ◦reduced tumor growth, size and weight ◦reduced Th17 cells in the tumor ◦reduced e-cadherin and growth factors (TGF-b) ◦increased beneficial bacteria with anti-inflammatory properties ◦increased IL-10 ◦increased HIF-1 expression	[100]
Sprague–Dawley rats exposed to DEN	HCC	VSL#3	Probiotic administration in rats with HCC: ◦inhibited the translocation of endotoxins and reduced intestinal inflammation ◦reduced bacterial dysbiosis and maintained intestinal integrity ◦decreased tumor growth and multiplicity	[84]
Effect of Probiotic Administration in Patients
Patients	Disease	Treatment/Probiotic	Effect	Reference
Obese children	NAFLD	VSL#3	Probiotic administration in children with cirrhosis: ◦reduced the severity of NAFLD ◦decreased HOMA and ALT levels ◦increased GLPp-1 and aGLP1	[101]
Patients with NAFLD or alcoholic liver disease	NAFLD or alcoholic liver cirrhosis	VSL#3	Probiotic administration in both patients with NAFLD or alcoholic liver disease: ◦improved plasma levels of MDA and 4-HNE ◦reduced levels of aspartate aminotransferase (AST) and ALT Probiotic administration in patients with alcoholic liver disease: ◦improved cytokine levels (TNF alpha, IL-6 and IL-10)	[102]
Patients with alcoholic psychosis	Alcohol-induced liver injury	B.bifidum and L.plantarum 8PA3	Probiotic administration in patients with alcoholic liver injury: ◦increased beneficial bacteria such as Bifidobacteria and Lactobacilli ◦reduced levels of AST and ALT	[103]
Patients with alcohol cirrhosis	Cirrhosis	L.casei Shirota (Lcs)	Probiotic administration in patients with alcoholic cirrhosis: ◦reduced sTNFR1, sTNRF2 and IL10 levels ◦reduced TLR2, 4 and 9 expressions ◦increased phagocytic capacity	[104]
Patients with cirrhosis and hepatic encephalopathy	Cirrhosis	VSL#3	Probiotic administration in patients with cirrhosis: ◦reduced episodes of hepatic encephalopathy ◦reduced hospitalization risk ◦improved Child–Turcotte–Pugh and model for end-stage liver disease scores	[105]
Patients with cirrhosis	Cirrhosis	E.coli Nissle	Probiotic administration in patients with cirrhosis: ◦increased beneficial bacteria such as Lactobacillus sp. and Bifidobacterium sp. ◦decreased potential pathogenic bacteria ◦reduced endotoxemia and bilirubin levels ◦improved liver functions evaluated by Child–Pugh score	[106]
Effect of FMT Administration in Rodents
Model	Disease	Treatment/FMT	Effect	Reference
Sprague–Dawley rats exposed to CCL4	Hepatic encephalopathy	FMT form healthy donor	FMT administration in rats with hepatic encephalopathy: ◦prevented hepatic necrosis ◦reduced intestinal mucosal barrier damage and intestinal permeability ◦improved hepatic encephalopathy grades and behavior ◦reduced TLR4 and TLR9 expression ◦decreased IL-1b, IL-6 and TNF alpha levels	[107]
C57Bl/6 mice exposed to ethanol	Alcoholic liver disease	FMT from alcohol-resistant donor mice	FMT administration in mice with alcoholic liver disease: ◦avoided bacterial dysbiosis ◦restored gut homeostasis ◦prevented steatosis and liver inflammation	[108]
C57Bl/6 mice under a HFD	NASH	FMT from healthy donor	FMT administration in mice with NASH: ◦increased of beneficial bacteria Christensenellaceae and Lactobacillus ◦improved tight junctions and endotoxemia ◦reduced lipid accumulation, proinflammatory cytokines and NAS score	[109]
Effect of FMT Administration in Patients
Patients	Disease	Treatment/FMT	Effect	Reference
Patients with metabolic syndrome	metabolic syndrome	FMT form healthy donor	FMT administration in patients with metabolic syndrome: ◦increased insulin sensitivity ◦increased butyrate-producing intestinal microbiota ◦decreased fecal short fatty acids	[110]
Patients with cirrhosis and Hepatic encephalopathy	Cirrhosis and Hepatic encephalopathy	FMT from donor with the optimal microbiota deficient in Hepatic encephalopathy	FMT administration in patients with cirrhosis and hepatic encephalopathy: ◦improved cognitive function ◦increased beneficial bacteria Lactobacillaceae, Bifidobacteriaceae ◦increased Ruminococcaceae	[111]
Patients with decompensated cirrhosis and hepatic encephalopathy	Cirrhosis and Hepatic encephalopathy	FMT from a donor enriched in Lachnospiraceae and Ruminicoccaceae	FMT administration in patients with cirrhosis and hepatic encephalopathy: ◦restored antibiotic-associated disruption in microbial diversity and function ◦increased abundance of Neisseriaceae and Pasteurellaceae ◦reduced Bifidobacteriaceae, Lachnospiraceae and Ruminococcaceae	[112]
Patients with advanced cirrhosis	Cirrhosis	FMT from healthy donors	FMT administration in patients with advanced cirrhosis: ◦was demonstrated to be safe ◦reduced ammonia plasma levels	[113]