Bile acids and microbes in metabolic disease

Table 1 Metabolic diseases caused by altered bile acid–gut microbiome interactions

No.	Model	Findings	Ref.
1	A T1DM clinical study	The abundance of Alistipes shahii, Asaccharobacter celatus, Blautia obeum, Coprococcus eutectic, Coprobacillus cateniforms, Clostridium symbiosum, and Eggerthella lenta significantly increased in adolescents with T1DM. Compared with healthy adolescents, the biosynthesis of vitamins, amino acids, electron carriers, and enzyme cofactors was downregulated, whereas fermentation pathways were upregulated in adolescents with T1D	[150]
2	An HFD-fed obese mouse model	Non-12-OH BA levels were higher in HF-OR mice. The levels of non-12-OH BASs, such as UDCA, CDCA, and LCA, decreased in HF-OP mice and were linked to changed gut flora. The abundance of C. scindens were reduced in HF-OP mice and positively correlated with UDCA and LCA. The administration of C. scindens to animals increased the levels of hepatic non-12-OH BAs and serum 7-hydroxy-4-cholesterin-3-one (C4). Changes in BA composition in HF-OP mice were associated with considerably lower GLP-1 expression levels in the ileum and PGC1 and UCP1 expression levels in brown adipose tissues	[18]
3	Patients with GDM and germ-free mice	The abundance of Bacteroides and Akkermansia decreased and that of Faecalibacterium increased with hyperglycemia	[151]
4	Women with GDM: A clinical study	The relative abundance of Streptococcus, Faecalibacterium, Veillonella, Prevotella, Haemophilus, and Actinomyces significantly increased with an increase in FBG levels and hyperlipidemia	[51]
5	A combination of BAs with dietary lard feeding in C57BL/6N mice	Impaired glucose tolerance; lower fasting insulin levels; lower counts of enteroendocrine cells; fatty liver; and elevated levels of hepatic TGs, cholesteryl esters, and monounsaturated fatty acids were noted. The relative abundance of Lachnospiraceae decreased and that of Desulfovibrionaceae, Clostridium lactatifermentans, and Flintibacter butyricus increased	[152]
6	A T2DM clinical study	Postprandial total BAs levels increased with an increase in the meal fat content and peaked after 1-2 h. Unconjugated and glycine-conjugated forms of DCA, CA, and UDCA were altered and FGF-19 levels were reduced in participants with T2DM	[153]
7	HFD-fed C57BL/6J mice with Enterobacter cloacae B29	Obesity and IR were induced	[45]
8	A T2DM clinical study	BAs increased twofold, and more hydrophobicity and higher 12α-hydroxy/non-12α-hydroxy BAs ratios were linked with lower insulin sensitivity and higher plasma TG levels	[154]
9	C57BL/6J ob/ob mice, lean ob/+, and HFD-fed mice	The abundance of A. muciniphila decreased in mice who were obese and had T2DM	[32]
10	A clinical study	The postprandial total bile acid response decreased in obese participants	[155]
11	Pregnancy with obesity: A clinical study	The abundance of Bifidobacterium and Bacteroides decreased and that of Staphylococcus, Enterobacteriaceae, and E. coli increased in overweight pregnant women compared with that in normal-weight pregnant women. The abundance of E. coli was higher in women with excessive weight gain than in those with normal weight gain during pregnancy. Bifidobacterium and A. muciniphila showed an opposite trend. The abundance of total bacteria, Staphylococcus, Bacteroides, Bifidobacterium, Enterobacteriaceae, and E. coli increased and that of Bifidobacterium decreased	[22]
12	ApoA-1-knockout mice, HFD-fed mice, and wild-type mice	Gut barrier-protecting Bifidobacterium species were absent, and impaired glucose tolerance was significantly increased	[27]
13	Zucker rats (obese/lean)	Increased numbers of Halomonas and Sphingomonas species, plasma LDL and VLDL levels, and reduced urinary hippurate and creatinine levels were noted in obese rats	[156]
14	Overweight pregnant women: A clinical study	Increased numbers of Bacteroides and Staphylococcus species were noted in obese pregnant women	[29]
15	HFD-fed mice	The abundance of intestinal gram-negative and gram-positive bacteria and Bifidobacterium species significantly decreased and endotoxemia significantly increased	[146]
16	C57BL/6J ob/ob mice, lean ob/+, and wild-type mice	A 50% reduction was noted in the abundance of Bacteroidetes, and an increase was noted in the abundance of Firmicutes	[157]

ApoA-1: Apolipoprotein A-1; A. muciniphila: Akkermansia muciniphila; BAs: Bile acids; BASs: Bile acid sequestrants; C4: 7α-hydroxy-4-cholesten-3-one; CA: Cholic acid; CDCA: Chenodeoxycholic acid; C. scindens: Clostridium scindens; DCA: Deoxycholic acid; E. coli: Escherichia coli; FGF-19: Fibroblast growth factor 19; FBG: Fasting blood glucose; GDM: Gestational diabetes mellitus; GLP-1: Glucagon-like peptide-1; HFD: High-fat diet; LCA: Lithocholic acid; LDL: Low-density lipoprotein; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; TGs: Triglycerides; UDCA: Ursodeoxycholic acid; VLDL: Very-low-density lipoprotein.