Microbiota-based treatments in alcoholic liver disease

Table 1 Microbiota-based treatment with probiotics in alcoholic liver disease - clinical trial

Patients	Enroll criteria or alcohol amount	Treatment	Results	Ref.
Compensated LC	Liver biopsy	Escherichia coli Nissle	Lactobacillus and Bifidobacterium sp. ↑	[70]
[alcohol: 22 (56.4%)]	Biochemical study	(2.5-25 × 109 for 42 d)	Proteus hausei and Citrobacter sp. ↓
Age = 53	Endotoxin level		Morganella sp. and endotoxemia ↓
M/F = 1.8:1	Stool microbiota		improvement of liver functions
Alcohol-related psychosis	Consumed 750 mL of Russian vodka (40% ethanol, daily)	Bifidobacterium bifidum	Bifidobacteria and Lactobacilli ↑	[71]
[66 (73.3%)]		(0.9 × 108 CFU for 5 d)	AST and ALT ↓
Age = 42.3 ± 1.1		Lactobacillus plantarum 8PA3 (0.9 × 109 CFU for 5 d)
All males
LC	LC	Lactobacillus casei Shirota	Neutrophil phagocytic capacity ↑	[72]
[alcohol: 12 (48%)]		(19.5 × 109 CFU for 28 d)	sTNFR1 ↓
Age = 51.2 ± 1.8			sTNFR2 ↓
M/F = 2:1			IL10 ↓
			TLR4 ↓
AH [60 (51.3%)]	AST/ALT > 1	Lactobacillus subtilis, Streptococcus faecium	Serum LPS level ↓	[74]
Age = 52.7 ± 11.3	AST and ALT level ↑	(1500 mg/d for 7 d)	TNF-α↓
M/F = 5.3:1	Alcohol intake
	> 40 g/d for female
	> 60 g/d for male

LC: Liver cirrhosis; AH: Alcoholic hepatitis; ALT: Alanine transaminase; AST: Aspirate transaminase; IL: Interleukin; sTNFR: Soluble tumor necrosis factor; TNF: Tumor necrosis factor; M: Male; F: Female; LPS: Lipopolysaccharide; CFU: Colony forming unit.

Table 2 Microbiota-based treatment in alcoholic liver disease - animal studies

Animal model	Alcohol amount	Treatment	Results	Ref.
6-wk-old male 10 C57BL/6 mice	Lieber-DeCarli liquid diet with 10% alcohol for 6 wk	Lactobacillus rhamnosus R0011, Lactobacillus acidophilus R0052	TLR-4 ↓	[75]
		(1 mg/mL per day for 4 wk)	IL-1β↓
4-wk-old male 20 C57BL/6 mice (10 Normal diet, 10 High-fat diet)	Oral administration 5 g/kg per day, twice/wk, for 9 wk	Lactobacillus rhamnosus R0011, Lactobacillus acidophilus R0052	In normal diet groups	[76]
		(1 mg/mL per day for 2 wk)	TNF-α↓
			IL-1↓
			TLR4 ↓
			TLR4/GADPH ↓
			In high-fat diet groups: IL-10 ↑
Male Sprague-Dawley rats	Dose gradually increased every 2 to 3 d up to a maximum of 8 g/kg per day by 2 wk	Oats (10 g/kg per day)	Tight junctions in colon ↓	[79]
			Disorganization of actin cytoskeleton ↓
	6 g/kg per day for final 10 wk		Oxidative stress ↓
			NO overproduction ↓
			Oxidative tissue damage ↓
			Nitrotyrosine ↓
			Carbonyl ↓

GAPDH: Glyceraldehyde-3-phospate dehydrogenase; IL: Interleukin; NO: Nitrooxidative; TLR: Toll-like receptor; TNF: Tumor necrosis factor.

Table 3 Microbiota-based treatment with prebiotics and antibiotics in alcoholic liver disease-clinical trial

Patients	Enroll criteria or alcohol amount	Treatment	Results	Ref.
HE	≥ two episodes of overt HE (Conn score ≥ 2)	Rifaximin	Episode of encephalopathy ↓	[16]
[alcohol 140 (46.8%)]	LC (MELD ≤ 25)	(1100 mg/d, for 6 mo)	(HR = 0.42)
Age = 56 ± 10
M/F = 1.2:1
LC with subclinical HE	Psychometric tests	Lactulose (45 mL/d for 8 wk)	Number of the abnormal psychometric test ↓	[80]
[alcohol 36 (48%)]	-Trail making test A
Age = 62.0 ± 7.3	-Wechsler adult intelligence scale		Prevalence of subclinical HE ↓
M/F = 1.2:1	-Symbol digit
	-Block design tests
LC	Laboratory investigations	Norfloxacin (800 mg/d)	Small-intestinal motor activity ↑	[82]
[alcohol 12 (35.3%)]	-Liver biopsy	Neomycin (1500 mg/d) alternating periods of 15 d for 6 mo	Transit time ↓
Age = 57.6	-Endoscopy		Small intestinal bacterial overgrowth ↓
M/F = 0.8:1			Child-Pugh Score ↓
TC	For LC	Rifaximin	Platelet count ↑	[83]
[alcohol 13 (56.5%)]	-Liver biopsy	(1200 mg/d, for 4 wk)	Endotoxin ↓
Age = 58 ± 3	-Laboratory findings		IL-1 ↓
M/F = 11.5:1	For hematological indices		IL-6 ↓
	-Platelet count ≤ 150000/μL		TNF-α↓

HE: Hepatic encephalopathy; IL: Interleukin; LC: Liver cirrhosis; PT: Patient; TC: Thrombocytopenic cirrhosis; TNF: Tumor necrosis factor.