Gut microbiota and liver diseases

Table 1 Composition of gut microbiota[1]

Microorganism	Stomach	Jejunum	Ileum	Colon
Total count	0-104	0-105	104-108	1010-1012
Aerobic microorganisms
Streptococcus	0-103	0-104	102-104	103-105
Enterococcus	rare	0-102	102-104	105-1010
Staphylococcus	0-103	0-103	102-105	104-106
Enterobacteria	0-102	0-103	102-107	104-1010
Anaerobic microorganisms
Peptostreptococcus	0-103	0-103	102-106	1010-1012
Bifidobacterium	0-102	0-104	103-109	108-1011
Lactobacillus	0-103	0-104	102-105	106-108
Clostridium	rare	rare	102-104	106-109
Eubacterium	rare	rare	rare	109-1012
Veillonella	0-102	0-103	102-104	103-106
Fusobacterium	0-102	0-103	103-104	106-108
Bacteroides fragillis	rare	0-103	103-107	1010-1012
Prevotella	0-102	102-104	103-104	104-105

Table 2 Changes in gut microbiota in human diseases[35]

Diseases	Change in microbiota
Allergies	Lactobacillus spp. ↓
	Bifidbacterium adolescentis↓
	Clostridium difficile↓
	Helicobacter pylori↓
Autism	Bacteroidetes↑
	Proteobacteria↑
	Actinobacteria↓
	Firmicutes↓
Obesity	Bacteroidetes↓
	Lactobacillus↑
	Firmicutes/Bacteroidetes ratio ↓
Type 2 Diabetes	Firmicutes↓
	Clostridia↓
	Betaproteobacteria↓
	Bacteroidetes/Firmicutes ratio ↑
Celiac disease	Bacteroides vulgatus↑
	Escherichia coli↓
	Clostridium coccoides↓

Table 3 Changes in gut microbiota in liver diseases

Diseases	Change in microbiota	Ref.
NAFLD	Bacteroidetes↓
	Prevotella↑	[41]
	Porphyromonas↑
Cirrhosis	Enterobacteriaceae↑
	Streptococcaceae↑	[45,46]
	Bifidobacteria↓
	Lachnospiraceae↓
	Bacteroidetes↓
	Firmicutes↓	[47]
	Streptococcus spp. ↑
	Veillonella spp. ↑
Alcoholics	Bacteroidaceae↓	[50,51]
	Prevotellaceae↑
Alcoholic liver cirrhosis	Enterobactericaea↑	[53]
Cirrhosis with encephalopathy	Porphyromonadacae↑	[55]
	Alcaligenacae↑

NAFLD: Nonalcoholic fatty liver disease.

Table 4 Randomized controlled trials for hepatic encephalopathy

Ref.	Year	Sample size(treatment/placebo)	Treatment regimens	Duration	Favorable effects
12Loguercio et al[69]	1987	40 (20/20)	Enterococcus Lactic Acid bacteria strain SF68 vs lactulose	10 d	NH3↓
					Performance status: improved
2Loguercio et al[70]	1995	40 (21/19)	Enterococcus Lactic Acid bacteria strain SF68 vs lactulose	3 x 4 wk	NH3↓
					Psychometric test: improved
12Liu et al[71]	2004	55 (20/35)	Pediacoccus pentoseceus, Leuconostoc mesenteroides, Lactobacillus paracasei, and Lactobacillus plantarum with fermentable fibers vs fermentable fibers only or non-fermentable fiber	30 d	Endotoxemia ↓Child-Turcotte-Pugh classification: improved
2Malaguarnera et al[72]	2007	60 (30/30)	Bifidobacterium (subtype not available) with fructo-oligosaccharide (FOS) vs mix of vitamins	90 d	NH3↓
					Psychometric test: improved
12Bajaj et al[73]	2008	25 (17/8)	Streptococcus thermophilus, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacteria vs none	60 d	Psychometric test: improved
12Sharma et al[74]	2008	105 (70/35)	Streptococcus faecalis, Clostridium butyricum, Bacillus mesentricus, and Lactic acid bacillus with lactulose vs lactulose	30 d	NH3↓
					Psychometric test: improved
12Mittal et al[75]	2011 (2009)	160 (120/40)	VSL#3 (containing Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus) vs lactulose or placebo	3 mo	NH3 (arterial) ↓
1Malaguarnera et al[76]	2010	125 (63/62)	Bifidobacterium (subtype not available) and FOS vs lactulose	60 d	NH3↓
					Psychometric test: improved
1Pereg et al[77]	2011	40 (20/20)	Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium bifidum, and Streptococcus thermophiles (Bio-plus, Supherb, Israel) vs placebo	6 mo	NH3↓
Agrawal et al[80]	2012	235 (157/78)	VSL#3 vs lactulose or none	> 3 mo	NH3 (arterial) ↓
					Psychometric test: improved
					Secondary prophylaxis of HE
Lunia et al[81]	2014	160 (86/74)	VSL#3 vs placebo	> 6 mo	NH3 (arterial) ↓
					Prevention of HE

¹RCTs included in meta-analysis by McGee et al[78];

²RCTs included in meta-analysis by Holte et al[79].

Table 5 Randomized controlled trials for non-alcoholic steatohepatitis

Ref.	Year	Sample size (treatment/placebo)	Treatment regimens	Duration	Favorable effects	Other information
1Aller et al[90]	2011	28 (14/14)	Lactobacillus bulgaricus and Streptococcus thermophiles vs placebo	3 mo	ALT ↓	Cardiovascular risk factors: NS
1Vajro et al[91]	2011	20 (10/10)	Lactobacillus rhamnosus strain GG vs placebo	8 wk	ALT ↓	Hepatorenal US ratio: NS
					PG-PS IgA ↓
1Malaguarnera et al[92]	2012	66 (34/32)	Bifidobacterium longum with fructo-oligosaccharides vs placebo	24 wk	ALT ↓ CRP ↓ TNF-α↓
					LDL-cholesterol ↓
					Serum endotoxin ↓
					HOMA-IR↓ Steatosis ↓
					NASH activity index ↓
1Wong et al[93]	2013	20 (10/10)	Lactobacillus plantarum, Lactobacillus deslbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium bifidum (The Lepicol probiotic formula) vs usual care	6 mo	AST ↓
					Liver fat (IHTG) ↓

¹RCTs included in meta-analysis by Ma et al[94]. PG-PS: Peptidoglycan-polysaccharide; IHTG: Intrahepatic triglyceride content; NASH: Non-alcoholic steatohepatitis; NS: Not significant.