Gut microbiota differences, metabolite changes, and disease intervention during metabolic - dysfunction - related fatty liver progression

Table 1 The production pathways of different short-chain fatty acids

	Related microorganisms	Way	Mechanism of action
Acetate[5,25,26,29,84,94]	Holdemanella	Acetyl-CoA pathway	(1) Improve mitochondrial modification and activate AMP-activated protein kinase to enhance fat oxidation[23]; (2) Activate GPR43 receptor[27]; and (3) Provide energy for organisms and synthesize cholesterol and lipids[26]
	F. prausnitzii
	Lachnospiraceae
	Ruminococcus
	Bifidobacterium
	Bacteroides
	Streptococcus
	Clostridum	The Wood-ljungdahl pathway
Propionate[5,22,25,26,84,94,95]	F. prausnitzii	Succinate pathway and acrylate pathway	(1) Enhance fatty-acid oxidation and reduce hepatic lipid accumulation[15]; (2) Activate GPR43 and GPR41 receptors[28]; and (3) Participate in the regulatory metabolism of gluconeogenesis[26]
	Prevotella
	Bacteroides
	Megasphaera elsdenii
	Dalister succinatiphilus
	Ruminococcus
	Veillonella
	Phascolarctobacterium
	Coprococcus
	Roseburia	Propylene glycol pathway
	Salmonella
	Akkermansia municiphilla
Butyrate[15,22,25,26,84,95,96]	Eubacteriota	Acetyl-coa pathway	(1) The energy source for the intestinal mucosa, promote the expression of tight junction proteins, and prevent "intestinal leakage"[97]; (2) Reduce the secretion of pro-inflammatory factors[25]; (3) Induce fat oxidation and attenuate the activation of HSC[16,36,37]; and (4) Activate GPR43 and GPR41 receptors[28]
	Clostridial cluster IV and XIVa
	Dalister succinatiphilus
	Oscillibacter
	Dorea
	F. prausnitzii
	Roseburia spp
	Ruminococcus
	Eubacterium rectale
	Coprococcus	Phosphotransbutyrylase/butyrate kinase pathway
	Anaerobutyricum
	Subdoligranulum
	Roseburia

F. prausnitzii: Faecalibacterium prausnitzii; HSC: Hepatic stellate cell.

Table 2 Probiotics regulate the gut microbiota and related disease factors

Probiotics	Phylum (Gram negative/positive)	Changes	Function
Bacillus subtilis + Enterococcus faecium[78]	Firmicutes (G+)	Firmicutes/Bacteroidetes↓	IL-1β, IL-6, TNF-α↓
		Akkermansia, Ruminococcus_UCG-014, Eubacterium_coprostanoligenes_group↑	TLR4, NF-κB↓
		Lachnoclostridium, Oscillibacter, Family_XIII_AD3011_group, Anaerovorax, Acetatifactor, Coriobacterium_UCG-002, Negativibacillus, Angelakisella, Ruminococcus, Harryflintia, Escherichia-Shigella↑	LPS↓
Lactobacillus acidophilus KLDS1.0901[77]	Firmicutes (G+)	Roseburia, Lachnospiraceae UCG-006, Bacteroides, Enterorhabdus↓	IL-1β, IL-6, TNF-α, LPS, Lactic acid↓
		Blautia, Alistipes, Oscillibacter, Faecalibaculum, Ruminiclostridium, Lactobacillus, Ruminococcaceae UCG-009↑	IL-10↑
Lactobacillus plantarum NCU116[76]	Firmicutes (G+)	Allobaculum, Lactobacillus, Bifidobacterium↑	LPS↓
			Intestinal barrier intact
Bifidobacterium longum MG723, MG731[76]	Actinobacteria (G+)		F4/80, MCP-1, TGF-β, IL-1β, IL-18↓
			BAs↑
Bifidobacterium lactis, Bifidobacterium.longum DD98[76]	Actinobacteria (G+)		IL-6, IL-1β, TNF-α↓
Bifidobacterium longum R0175[76]	Actinobacteria (G+)	Alloprevotella spp.↑	IL-1, TNF-α, Chemokines↓
		Acetatifactor muris, Butyricimonas spp., Oscillibacter spp.↓
Bifidobacterium longum LC67[76]	Actinobacteria (G+)	Firmicutes, Proteobacteria, Tyzzerella, Escherichia-Shigella, Nestiinimonas, Osillibacter, Ruminiclostridium↓
		Faecalibacterium, Lactobacillus↑
Bifidobacterium bifidum[76]	Actinobacteria (G+)	Tyzzerella, Escherichia-Shigella, Nestiinimonas, Osillibacter↓	Propionate, butyrate↑
		Faecalibacterium, Ruminococcus↑
Lactobacillus paracasei Jlus66[98]	Actinobacteria (G+)	Firmicutes↑	IL-6, TNF-α, LPS↓
		Proteobacteria, Clostridia↓	IL-10↑
		Clostridiaceae, Oscillospiraceae, Bifidobacteriaceae↑
		Lactobacillus, Bifidobacterium↑
Lactiplantibacillus plantarum ZDY2013[75]	Actinobacteria (G+)	Lachnospirillaceae, Muribaculaceae, Lactobacillus spp., Alloprevotella and Blautia↑	LPS/NF-κB↓
		Fusobacteria, Verrucomicrobia↓	Tight binding protein, IR↑
Lactobacillus sakei MJM60958[79]	Actinobacteria (G+)	Salmonella gallinarum KCTC 2931, E. coli O1 KCTC 2441, Salmonella cholerae KCTC 2932, Pseudomonas aeruginosa KCCM 11802↓	Acetic acid↑
Akkermansia mucophila[23]	Verrucomicrobiota (G-)		γδT17, NF-κB, LPS↓
			Fat oxidation, Acetate, IL-10, Mucin (intestinal barrier integrity)↑
F. prausnitzii[84,86,87]	Firmicutes (G-)	Erysipelatoclostridium, Faecalibaculum, Blautia, Akkermansia, Bifidobacterium, Lactobacillus, Duboria↑	TNF-α, IL-1β, IL-6, TLR4↓
		Tyzzerella↓	Butyrate, intestinal barrier↑
Christensenella minuta[88]	Firmicutes (G-)		Acetate, butyrate↑
Bifidobacterium adolescentis[72]	Actinobacteria (G+)		Intestinal barrier↑
			TLR4/NF-κB, IL-6, IL-1β, TNF-α↓
Bacteroides ovatus[92]	Bacteroidetes (G-)	Lachnospiraceae_NK4A136_group, norank_f_Oscillospiraceae, Colidextribacterder↑	SCFA, intestinal barrier↑
		F/B, Ruminococcus_torques_group, Ruminococcus_gauvreauii_group, Erysipelothrix rhusiopathiae↓	LPS, CD163, IL-1β, TNF-α↓

F. prausnitzii: Faecalibacterium prausnitzii; E. coli: Escherichia coli; LPS: Lipopolysaccharide; BA: Bile acid; IR: Insulin resistance; SCFA: Short-chain fatty acid.