Fecal microbiota transplantation: A promising treatment strategy for chronic liver disease

Table 1 Clinical trials and animal studies on fecal microbiota transplantation for chronic liver disease treatment

Disease	Ref.	Year	Type	Comparison	Frequency	Key findings
MASLD/NAFLD	Zhou et al[20]	2017	Mice	Control vs HFD vs HFD + FMT	8 consecutive weeks	FMT mitigated HFD-induced steatohepatitis through its beneficial effects on intestinal microbiota
	García-Lezana et al[21]	2018	Rat	Autologous FMT vs allogenic FMT	Once	Allogeneic FMT led to a significant decrease in portal vein pressure
	Witjes et al[22]	2020	Human	Autologous FMT vs lean vegan donor FMT	3 times within eight weeks	After allogeneic FMT, the expression of hepatic genes related to lipid metabolism and inflammation was significantly reduced. The observed changes in intestinal microbiota composition were found to be connected to changes in plasma metabolites and markers
	Craven et al[23]	2020	Human	Autologous FMT vs allogenic FMT	Once	Patients who received allogeneic FMT showed a significant reduction in intestinal permeability after 6 weeks
	Xue et al[24]	2022	Human	Oral probiotics vs FMT + three enemas	Once	FMT effectively improved the therapeutic outcomes in NAFLD patients. It demonstrated greater efficacy in lean NAFLD patients than those with obesity
ALD	Llopis et al[11]	2016	Mice	SAH FMT vs alcoholism FMT	Once	Transplanting intestinal microbiota from mice with alcoholism, but without AH, alleviated alcohol-induced liver injury
	Ferrere et al[28]	2017	Mice	Pectin vs FMT	One per week	Manipulating the intestinal microbiota can prevent alcohol-induced liver injury, positioning it as a new therapeutic target for ALD
	Wolstenholme et al[29]	2022	Mice	Placebo vs FMT	Once	Mice in the FMT group reduced ethanol acceptance, intake, and preference
	Philips et al[30]	2017	Human	Case report	7 consecutive days	After FMT, clinical indicators, biochemical markers, and severity scores improved in SAH patients, with significant changes in intestinal microbiota observed
	Philips et al[31]	2017	Human	Control vs FMT	7 consecutive days	After FMT, there was a improvement in liver disease severity, an increase in survival rates, and notable changes in the composition of the intestinal microbiota
	Philips et al[32]	2018	Human	Corticosteroids vs nutrition vs pentoxifylline vs FMT	7 consecutive days	FMT showed a higher survival rate compared to other treatments for SAH, potentially serving as a cost-effective bridge to liver transplantation or improving survival without it
	Philips et al[33]	2022	Human	Pentoxifylline vs FMT	7 consecutive days	FMT improves 6-month survival and reduces liver-related complications, related to beneficial modulation of the gut microbiota
	Philips et al[34]	2022	Human	SOC vs FMT	7 consecutive days	FMT significantly reduces ascites, infections, encephalopathy, and alcohol relapse, with a trend toward higher survival, associated with beneficial modulation of the gut microbiota
	Sharma et al[35]	2022	Human	SOC vs FMT	Once	FMT is safe and could improve short- and medium-term survival rates, and clinical severity scores in patients with SAH-ACLF
	Pande et al[36]	2023	Human	Prednisolone vs FMT	28 consecutive days	FMT is safe, improves 90-day survival, and reduces infections by positively modulating microbial communities
CHB	Ren et al[39]	2017	Human	Antiviral therapy vs antiviral therapy + FMT	Once every 4 weeks, until HBeAg clearance was achieved	In patients with sustained positive HBeAg after long-term antiviral therapy, FMT can reduce or even eliminate HBeAg levels
	Chauhan et al[40]	2021	Human	Antiviral therapy vs antiviral therapy + FMT	Once every 4 weeks for a total of six times	FMT is safe and effective in HBeAg clearance in HBeAg-positive CHB patients
PSC	Philips et al[43]	2018	Human	Case report	Once a week for a total of four times	After FMT, significant changes were observed in the liver biochemistry, bile acids, and the composition of the intestinal microbiota in PSC patients
	Allegretti et al[46]	2019	Human	Control vs FMT	Once	The improvement in ALP levels may be linked to an increase in the diversity of the intestinal microbiota, as well as the frequency of FMT
AIH	Liang et al[47]	2021	Mice	Control vs FMT	28 consecutive days	FMT can alleviate liver injury and bacterial translocation, partially reverse the elevation of serum ALT and AST, restore the balance between follicular regulatory T and helper T cells in the spleen, and effectively correct the intestinal microbiota dysbiosis
Cirrhosis/HE	Wang et al[51]	2017	Rat	Control vs probiotics vs low-dose FMT vs moderate-dose FMT vs high-dose FMT	3 consecutive weeks	FMT prevents liver necrosis, improves behavioral performance, HE scores, and spatial learning ability in rats, enhances the expression of intestinal tight junction proteins, and repairs intestinal mucosal barrier damage. It also reduces the expression of TLR4 and TLR9 in the liver, along with a decrease in circulating pro-inflammatory factors (IL-1β, IL-6, TNF)
	Kao et al[52]	2016	Human	Case report	Once a week for 5 times	FMT can reverse intestinal microbiota dysbiosis and lead to the obvious improvement of cognitive function in dominant HE
	Bajaj et al[53]	2017	Human	SOC vs FMT + SOC	Once	FMT can reduce the hospitalization rate, improve cognitive function, and restore intestinal microbiota dysbiosis
	Bajaj et al[54]	2019	Human	SOC vs FMT + SOC	Once	Follow-up for more than one year demonstrated that the positive effects of FMT may be long-lasting
	Bajaj et al[55]	2019	Human	Placebo capsules vs FMT capsules	15 capsules	Oral FMT capsules are safe and well-tolerated. FMT is associated with improvements in duodenal mucosal diversity, intestinal microbiota dysbiosis, and AMP expression, along with a decrease in LBP levels and better performance in the brain App test
	Bajaj et al[56]	2019	Human	Placebo capsules vs FMT capsules	15 capsules	FMT has a beneficial effect on the intestinal microbiome function in patients with cirrhosis, leading to improvements in inflammation and cognitive performance. However, recipients with lower levels of secondary bile acids may experience poorer outcomes
	Bloom et al[57]	2022	Human	Case report	5 doses of 15 capsules within 3 weeks	FMT capsules improved cognitive performance in patients with HE, with the effect varying based on both donor and recipient factors
	Mehta et al[59]	2018	Human	Case report	Once	FMT can significantly reduce arterial ammonia concentrations, alleviate neurological symptoms, and lower CTP and MELD scores in patients with HE
	Li et al[60]	2022	Human	Case report	3 times	FMT can improve liver function, relieve clinical symptoms, and significantly reduce the number of HE episodes in patients
	Huang et al[61]	2021	Rat	Sham operation vs BDL vs BDL + FMT vs BDL + GMT	5 consecutive days	FMT increased the abundance of Bifidobacterium and significantly reduced portal vein pressure
	Bajaj et al[62]	2018	Human	SOC vs SOC + antibiotic + FMT	Once	FMT has also been shown to restore the diversity and function of the intestinal microbiota altered by antibiotics in patients with advanced cirrhosis who are treated with lactulose and rifaximin

ACLF: Acute on chronic liver failure; AH: Alcoholic hepatitis; AIH: Autoimmune hepatitis; ALD: Alcohol liver disease; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AMPs: Antimicrobial peptides; AST: Aspartate aminotransferase; BDL: Bile duct ligation; CHB: Chronic hepatitis B; CTP: Child-Turcotte-Pugh; FMT: Fecal microbiota transplantation; GMT: Transplantation of gut content from the terminal ileum; HBeAg: Hepatitis B e antigen; HE: Hepatic encephalopathy; HFD: High-fat diet; LBP: Lipopolysaccharide-binding protein; MASLD: Metabolic dysfunction-associate steatotic liver disease; MELD: Model for end-stage liver disease; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; PSC: Primary sclerosing cholangitis; SAH: Severe alcoholic hepatitis; SOC: Standard of care; TLRs: Toll-like receptors; TNF: Tumor necrosis factor.