. 2020 Jan;577(7790):410-415.
doi: 10.1038/s41586-019-1865-0.
Epub 2019 Dec 25.
Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
Affiliations
- PMID: 31875848
- PMCID: PMC7274525
- DOI: 10.1038/s41586-019-1865-0 (VSports app下载)
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"V体育2025版" Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
Nature.
2020 Jan.
Abstract
The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules1. Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins2 VSports手机版. Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors3,4. These receptors have pivotal roles in shaping host innate immune responses1,5. However, the effect of this host-microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3+ regulatory T (Treg) cells expressing the transcription factor RORγ. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this Treg cell population. Restoration of the intestinal BA pool increases colonic RORγ+ Treg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites. .
Conflict of interest statement
Competing Interests
The authors declare no competing interests.
Figures
(a) Beginning at 3 weeks of age, 3 groups of mice were
fed special diets for 4 weeks. SPF mice were fed either a nutrient-rich or a
minimal diet, and GF mice were fed the nutrient-rich diet. Colonic Tregs
were analyzed, and absolute numbers of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
are shown. (b, c) Three-week-old SPF mice were fed
as in a, and Tregs in different tissues were analyzed after 4
weeks. Representative plots (b) and frequencies of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
(c) are shown. iLN, inguinal lymph nodes; mLN, mesenteric
lymph nodes; PP, Peyer’s patches. (d-f) SPF
mice were fed a nutrient-rich diet or a minimal diet at birth and were
either maintained on that diet or switched to the opposite diet at 3 weeks
of age. Colonic Tregs were analyzed after 4 weeks. Representative plots of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
(d), frequencies of Foxp3+ in the
CD4+TCRβ+ cell population (e),
and RORγ+Helios– in the colonic
Foxp3+CD4+TCRβ+ Treg population
(f) are shown. (g-i) LC/MS
quantitation of fecal acetate (g), propionate (h),
and butyrate (i) from SPF mice fed a nutrient-rich diet, or a
minimal diet, and from GF mice fed a nutrient-rich diet. (j)
Three-week-old SPF mice were fed a nutrient-rich diet, a minimal diet, or a
minimal diet supplemented with individual or mixed SCFAs in drinking water.
Colonic Tregs were analyzed after 4 weeks. Frequencies of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
are shown. Data are representative of two independent experiments.
n represents biologically independent animals. In
a, c, e-j, bars
indicate mean ± SEM values. ∗p < 0.05,
∗∗p < 0.01, and ∗∗∗p <
0.001 in one-way analysis of variance followed by the Bonferroni post hoc
test in a, e-i, or ∗∗p
< 0.01 in two-tailed Student’s t test in
c.
(a, b) Absolute numbers of
RORγ+Helios– in the colonic
Foxp3+CD4+TCRβ+ Treg population
(a) and of Foxp3+ Tregs in the
CD4+TCRβ+ population (b) in
SPF mice fed a nutrient-rich diet, a minimal diet, or a minimal diet
supplemented with mixtures of primary or secondary BAs in drinking water.
The primary BAs were cholic acid (CA), chenodeoxycholic acid (CDCA), and
ursodeoxycholic acid (UDCA) (2 mM of each). The secondary BAs were
3-oxo-cholic acid (3-oxo-CA), 3-oxo-lithocholic acid (3-oxo-LCA),
7-oxo-cholic acid (7-oxo-CA), 7-oxo-chenodeoxycholic acid (7-oxo-CDCA),
12-oxo-cholic acid (12-oxo-CA), 12-oxo-deoxycholic acid (12-oxo-DCA),
deoxycholic acid (DCA), and lithocholic acid (LCA) (1 mM of each).
(c) Three-week-old SPF mice were fed a nutrient-rich diet,
a minimal diet, or a minimal diet supplemented with one or more primary or
secondary bile acids in drinking water. Colonic Th17 cells were analyzed
after 4 weeks. CA, CDCA, UDCA, DCA, LCA, 3-oxo-CA, 3-oxo-LCA, 7-oxo-CA,
7-oxo-CDCA, 12-oxo-CA, 12-oxo-DCA, and the indicated BA combinations were
tested. Frequencies of RORγ+Foxp3– in
the CD4+TCRβ+ population are shown.
(d, e) Three-week-old SPF mice were fed a
nutrient-rich diet, a minimal diet, or a minimal diet supplemented with the
indicated primary BAs (CA/CDCA/UDCA, 2 mM of each) or secondary BAs
(Oxo-BAs/LCA/DCA, 1 mM of each) in drinking water. Tregs and Th17 cells in
spleen, mesenteric lymph node (mLN), and ileum were analyzed after 4 weeks.
Frequencies of RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
(d) and of RORγ+Foxp3–
in the CD4+TCRβ+ cell population
(e) are shown. Data are pooled from two or three
independent experiments. n represents biologically
independent animals. Bars indicate SEM values. ∗∗p <
0.01 and ∗∗∗p < 0.001 in one-way analysis of
variance followed by the Bonferroni post hoc test in a,
b.
(a-d) Three-week-old SPF mice were fed a
nutrient-rich diet or a minimal diet, and the microbial compositions in
colonic lumen were analyzed after 4 weeks by 16S rRNA sequencing. Observed
OTUs (a), Shannon index (b), PCoA analysis
(c), and relative abundance of bacteria at the phylum and
family levels (d) are shown. (e) Quantitative PCR
analysis of 16S rDNA of Clostridium cluster IV and
Clostridium cluster XIVα in colonic luminal
specimens from SPF mice fed a nutrient-rich diet, a minimal diet, or a
minimal diet supplemented with the indicated primary BAs (CA/CDCA/UDCA, 2 mM
of each) or secondary BAs (Oxo-BAs/LCA/DCA, 1 mM of each) in drinking water.
(f) Four-week-old GF mice or GF mice receiving transferred
fecal materials (FMT) from minimal-diet or rich-diet SPF mice were fed a
nutrient-rich diet or a minimal diet, and colonic Tregs were analyzed after
2 weeks. Frequencies of colonic
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
are shown. Data are pooled from three independent experiments in
a-d. Data are representative of two
independent experiments in e, f.
n represents biologically independent animals. Bars
indicate mean ± SEM value, and ∗∗∗p <
0.001 in one-way analysis of variance followed by the Bonferroni post hoc
test.
(a) Schematic diagram of pNJR6 suicide
vector–mediated BA gene deletion in Bacteroides.
(b) Genotyping of B.
thetaiotaomicron and B.
fragilis BA metabolic pathway mutants by PCR. PCR
primers were designed to target the flanking regions of an intact gene. PCR
of an untouched gene plus its flanking regions generated a PCR product of
~1150–1500 bp, while deletion of an interested BA metabolic gene
resulted in only a ~350- to 450-bp PCR amplicon of its two flanking regions.
(c, d) Bacterial load (measured as CFU/g of
feces) of B. thetaiotaomicron (c) and
B. fragilis (d) BA metabolic pathway
mutants and their wild-type (WT) control strains in monocolonized GF mice.
(e, f) LC/MC quantitation of fecal conjugated
primary BAs (e) and deconjugated primary BAs (f)
in GF mice monocolonized with B.
thetaiotaomicron or B.
fragilis BA metabolic pathway mutants and their
wild-type (WT) control strains. Data are representative of two independent
experiments in b, e, f. Data are
pooled from three independent experiments in c, d.
n represents biologically independent animals. Bars
indicate mean ± SEM values in c-f.
(a, b) Each of 4 groups of GF mice was
colonized with one of the following microbes: 1) a wild-type (WT) strain of
B. thetaiotaomicron; 2) a BSH mutant
strain; 3) a 7α-HSDH mutant strain; or 4) a triple-mutant strain.
Colonic Tregs were analyzed after 2 weeks. Absolute numbers of
RORγ+Helios– in the colonic
Foxp3+CD4+TCRβ+ Treg population
(a) and of Foxp3+ Tregs in the
CD4+TCRβ+ population (b) are
shown. (c, d) Each of 4 groups of GF mice was
colonized with one of the following microbes: 1) a WT strain of
B. fragilis; 2) a BSH KO strain; 3) a
7α-HSDH KO strain; or 4) a double-mutant strain. Absolute numbers of
colonic Tregs are shown as in a, b.
(e, f) GF mice were colonized with
B. thetaiotaomicron BA metabolic
pathway mutants or their wild-type (WT) control strains. Colonic Tregs and
Th17 were analyzed after 2 weeks. Frequencies of Foxp3+ in the
CD4+TCRβ+ cell population (e)
or RORγ+Foxp3– in the
CD4+TCRβ+ cell population (f)
are shown. (g, h) GF mice were colonized with
B. fragilis BA metabolic pathway
mutants or their wild-type control strains. Frequencies of colonic Tregs and
Th17 are shown as in e, f. (i,
j) GF mice were colonized with B.
thetaiotaomicron BA metabolic pathway mutants or their
wild-type (WT) control strains. Tregs and Th17 cells in the spleen,
mesenteric lymph node (mLN), and ileum were analyzed after 2 weeks.
Frequencies of RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
(i) and RORγ+Foxp3– in
the CD4+TCRβ+ cell population (j)
are shown. (k, l) GF mice were colonized with
B. fragilis BA metabolic pathway
mutants or their wild-type control strains. Frequencies of Tregs and Th17 in
spleen, mLN, and ileum are shown as in i, j. Data
are pooled from two or three independent experiments. n
represents biologically independent animals. Bars indicate mean ± SEM
values. ∗p < 0.05, ∗∗p < 0.01, and
∗∗∗p < 0.001 in one-way analysis of variance
followed by the Bonferroni post hoc test in a,
c.
(a) Protein expression of VDR, FXR (NR1H4), and GPBAR1
in the colonic tissue of SPF C57BL/6J mice was analyzed by western blot. The
red asterisks indicate the corresponding molecular weight of VDR (53 kDa),
FXR (69 kDa), and GPBAR1 (33 kDa). For gel source data, see Supplementary Figure 1.
(b, c) Absolute numbers of
RORγ+Helios– in the colonic
Foxp3+CD4+TCRβ+ Treg population
(b) and of Foxp3+ Tregs in the
CD4+TCRβ+ population (c) from
mice deficient in nuclear receptors
(Nr1i2–/–Nr1i3–/–,
Nr1h3–/–,
Vdr–/–,
Nr1h4–/–, and
Vdr–/–Nr1h4–/–)
and their littermate controls. (d, e) Frequencies
of Foxp3+ in the CD4+TCRβ+ cell
population from mice deficient in G protein-coupled receptors
(Gpbar1–/–,
Chrm2–/–,
Chrm3–/–, and
S1pr2–/–) and their littermate
controls (d) and from mice deficient in nuclear receptors
(Nr1i2–/–Nr1i3–/–,
Nr1h3–/–,
Vdr–/–,
Nr1h4–/–, and
Vdr–/–Nr1h4–/–)
and their littermate controls (e). (f,
g) Frequencies of
RORγ+Foxp3– in the
CD4+TCRβ+ cell population from mice
described in d, e. (h-n)
Tregs in the spleen, mesenteric lymph node (mLN), and ileum from the
indicated mice were analyzed. Frequencies of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population
from Gpbar1–/– (h),
Chrm2–/– (i),
Chrm3–/– (j),
S1pr2–/– (k),
Nr1i2–/–Nr1i3–/–
(l), Nr1h3–/–
(m), and Vdr–/–,
Nr1h4–/–, and
Vdr–/–Nr1h4–/–
(n) mice and their littermate controls are shown. Data are
representative of two or three independent experiments in a,
d-n, or are pooled from two or three
independent experiments in b, c.
n represents biologically independent animals. Bars
indicate mean ± SEM values. ∗∗p < 0.01 in
one-way analysis of variance followed by the Bonferroni post hoc test in
b.
(a, b) Beginning at 3 weeks of age, 3
groups of mice were fed special diets for 4 weeks. SPF mice were fed either
a nutrient-rich or a minimal diet, and GF mice were fed the nutrient-rich
diet. The levels of 1,25-dihydroxyvitamin D3 in serum (a) and
colon (b) of these mice were determined by ELISA.
(c) SPF mice were fed a nutrient-rich diet or a vitamin D3
or a vitamin A deficient-rich diet at birth. Colonic Tregs were analyzed
after 7 weeks. Frequencies of
RORγ+Helios– in the colonic
Foxp3+CD4+TCRβ+ Treg population
are shown. (d) SPF mice were fed a nutrient-rich-diet at birth
and were either maintained on that diet or switched to a vitamin D3 or
vitamin A-deficient rich diet at 3 weeks of age. Colonic Tregs were analyzed
after 4 weeks. Frequencies of
RORγ+Helios– in the colonic
Foxp3+CD4+TCRβ+ Treg population
are shown. Data are representative of two independent experiments.
n represents biologically independent animals. Bars
indicate mean ± SEM values. ∗∗∗p < 0.001
in one-way analysis of variance followed by the Bonferroni post hoc test in
c, d.
Volcano plots comparing transcriptomes of colonic Tregs from
Vdr+/+Foxp3mRFP
and
Vdr–/–Foxp3mRFP
mice (n = 3). Colonic RORγ+ Treg
signature genes are highlighted in red (up-regulated) or blue
(down-regulated). The number of genes from each signature preferentially
expressed by one or the other population is shown at the bottom. Data are
pooled from two independent experiments. n represents
biologically independent animals. To determine the enrichment of certain
gene signatures in RNA-seq data sets, a Chi-square test was used. p values
of < 0.05 were considered statistically significant.
(a-c) Three-week-old SPF mice were fed a
nutrient-rich diet, a minimal diet, or a minimal diet supplemented with
mixtures of primary BAs (CA/CDCA/UDCA, 2 mM of each) or secondary BAs
(Oxo-BAs/LCA/DCA, 1 mM of each) in drinking water. Initial body weights were
recorded before DSS challenge (a). Clinical scores
(b) and hematoxylin and eosin histology (c)
for representative colons from mice not challenged with DSS are shown.
(d, e) Three-week-old SPF mice fed a
nutrient-rich diet or a minimal diet for 4 weeks were then challenged in the
DSS-induced colitis model. After the development of colitis at day 5 of the
model, the DSS containing drinking water was switched to regular drinking
water or to drinking water supplemented with mixtures of primary or
secondary BAs. The primary BAs were CA, CDCA, and UDCA (2 mM of each). The
secondary BAs were 3-oxo-CA, 3-oxo-LCA, 7-oxo-CA, 7-oxo-CDCA, 12-oxo-CA,
12-oxo-DCA, DCA, and LCA (1 mM of each). Daily weight loss (d)
of mice during the course of DSS-induced colitis and clinical scores
(e) on day 10 of colitis are shown. Data are representative
of two independent experiments. n represents biologically
independent animals. Bars indicate mean ± SEM values in
a, b, d, e.
(a-c) Daily weight loss (a)
of Vdr+/+ and
Vdr–/– mice during the course
of DSS-induced colitis. Clinical scores (b) and hematoxylin and
eosin histology (c) of representative colons on day 10 of
colitis are shown. (d) Schematic representation of the T cell
adaptive transfer model of colitis.
Rag1–/– mice are transferred
with either Vdr+/+ or
Vdr–/– naïve T cells.
(e-g) Weight loss (e) of
Rag1–/– mice in d
during the course of T cell adaptive transfer-induced colitis. Clinical
scores (f) and hematoxylin and eosin histology (g)
of representative colons on day 67 of colitis are shown. Data are
representative of two independent experiments. n represents
biologically independent animals. Bars indicate mean ± SEM values in
a, b, e, f.
∗∗p < 0.01 and ∗∗∗p < 0.001
in two-way analysis of variance followed by the Bonferroni post hoc test in
a, e, or ∗p < 0.05 and
∗∗p < 0.01 in two-tailed Student’s
t test in b, f.
(a) Beginning at 3 weeks of age, 3 groups of mice were fed
special diets for 4 weeks. SPF mice were fed either a nutrient-rich or a minimal
diet, and GF mice were fed the nutrient-rich diet. Representative plots and
frequencies of RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population are
shown. (b–d) LC/MS quantitation of fecal
conjugated primary BAs (b), deconjugated primary BAs
(c), and secondary BAs (d) from groups of mice fed
as in a. The BAs determined were cholic acid (CA), chenodeoxycholic
acid (CDCA), ursodeoxycholic acid (UDCA), α-muricholic acid
(αMCA), β-muricholic acid (βMCA), deoxycholic acid (DCA),
lithocholic acid (LCA), 3-oxo-cholic acid (3-oxo-CA), 3-oxo-lithocholic acid
(3-oxo-LCA), 7-oxo-cholic acid (7-oxo-CA), 7-oxo-chenodeoxycholic acid
(7-oxo-CDCA), 12-oxo-cholic acid (12-oxo-CA), 12-oxo-deoxycholic acid
(12-oxo-DCA), ω-muricholic acid (ωMCA), and taurine-conjugated
species (TCA, TCDCA, TUDCA, TαMCA, and TβMCA). (e)
Three-week-old SPF mice were fed a nutrient-rich diet, a minimal diet, or a
minimal diet supplemented with one or more primary or secondary bile acids in
drinking water for 4 weeks. Representative plots and frequencies of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population and
of Foxp3+ in the CD4+TCRβ+ population
are shown. The BAs used in the feed were CA, CDCA, UDCA, DCA, LCA, 3-oxo-CA,
3-oxo-LCA, 7-oxo-CA, 7-oxo-CDCA, 12-oxo-CA, 12-oxo-DCA, and various indicated BA
combinations. Data are representative of at least two independent experiments in
a-d, Data are pooled from three independent
experiments in e. n represents biologically
independent animals. Bars indicate mean ± SEM values. ∗p <
0.05, ∗∗p < 0.01, and ∗∗∗p <
0.001 in one-way analysis of variance followed by the Bonferroni post hoc
test.
(a) Schematic diagram of BA metabolic pathways in
B. thetaiotaomicron and
B. fragilis. (b) Each of 4 groups
of GF mice was colonized with one of the following microbes for 2 weeks: 1) a
wild-type (WT) strain of B. thetaiotaomicron; 2) a BSH mutant
strain (BSH KO, in which both the BT_1259 and BT_2086 genes are deleted); 3) a
7α-HSDH mutant strain (7α-HSDH KO, in which the BT_1911 gene is
deleted); or 4) a triple-mutant strain (TKO, in which all three genes are
deleted). Representative plots and frequencies of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population are
shown. (c) Each of 4 groups of GF mice was colonized with one of
the following microbes for 2 weeks: 1) a WT strain of B.
fragilis; 2) a BSH KO strain (in which the BF638R_3610 gene is
deleted); 3) a 7α-HSDH KO strain (in which the BF638R_3349 gene is
deleted); or 4) a double-mutant strain (DKO, in which both genes are deleted).
Colonic Tregs were analyzed as in b. Data are pooled from three
independent experiments in b, c. n
represents biologically independent animals. Bars indicate mean ± SEM
values in b, c. ∗∗∗p <
0.001 in one-way analysis of variance followed by the Bonferroni post hoc
test.
(a) Quantitative mRNA expression of BA receptors in the
colon of SPF mice. (b) Frequencies of colonic
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population from
mice deficient in G protein–coupled receptors
(Gpbar1–/–,
Chrm2–/–,
Chrm3–/–, and
S1pr2–/–) and their littermate
controls. (c) Representative plots and frequencies of colonic
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population from
mice deficient in nuclear receptors
(Nr1i2–/–Nr1i3–/–,
Nr1h3–/–,
Vdr–/–,
Nr1h4–/–, and
Vdr–/–Nr1h4–/–),
their littermate controls, and minimal-diet
Vdr+/+Nr1h4+/+ mice.
(d) Three-week-old
Vdr+/+Nr1h4+/+,
Vdr–/–,
Nr1h4–/–, and
Vdr–/–Nr1h4–/–
mice were fed a minimal diet or a minimal diet supplemented with primary BAs
(CA/CDCA/UDCA, 2 mM of each) or secondary BAs
(DCA/LCA/3-oxo-CA/3-oxo-LCA/7-oxo-CA/7-oxo-CDCA/12-oxo-CA/12-oxo-DCA, 1 mM of
each) in their drinking water for 4 weeks. Frequencies of
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population are
shown. (e) Normalized expression values of Vdr in
colonic T conventional cells (Tconv), Foxp3+ Tregs, dendritic cells
(DC), and epithelial cells (Epith). (f) Normalized expression
values of Vdr in splenic Tregs (Sp Treg), colonic Tregs (Co
Treg), colonic RORγ− Tregs (Co
RORγ− Treg), and colonic RORγ+
Tregs (Co RORγ+ Treg). (g) Frequencies of colonic
RORγ+Helios– in the
Foxp3+CD4+TCRβ+ Treg population from
Vdrflox/floxFoxp3YFP-cre,
Vdrflox/floxCd11ccre,
Vdrflox/floxVil1cre
mice and from Vdrflox/flox and
Foxp3YFP-cre mice. (h) Volcano
plots comparing transcriptomes of colonic Tregs from
Vdr+/+Foxp3mRFP or
Vdr–/–Foxp3mRFP
mice (n = 3). Colonic Treg signature genes are highlighted in
red (up-regulated) or blue (down-regulated). Data are pooled from two or three
independent experiments. n represents biologically independent
animals. Bars indicate mean ± SEM values. ∗∗p < 0.01
and ∗∗∗p < 0.001 in one-way analysis of variance
followed by the Bonferroni post hoc test in c, d,
g or Chi-square test in h.
(a) Frequencies of
RORγ+Helios– in the colonic
Foxp3+CD4+TCRβ+ Treg population on
day 2 of DSS-induced colitis in mice fed a nutrient-rich diet, a minimal diet,
or a minimal diet supplemented with mixtures of primary or secondary BAs in
drinking water. The primary BAs were CA, CDCA, and UDCA (2 mM of each). The
secondary BAs were DCA, LCA, 3-oxo-CA, 3-oxo-LCA, 7-oxo-CA, 7-oxo-CDCA,
12-oxo-CA, and 12-oxo-DCA (1 mM of each). (b) Daily weight loss of
mice described in a during the course of DSS-induced colitis.
(c) Clinical scores and (d) hematoxylin and
eosin–stained histologic sections for representative colons on day 10 of
colitis (see b). (e) Daily weight loss of
Vdrflox/flox and
Vdrflox/floxFoxp3YFP-cre
mice during the course of DSS-induced colitis. (f) Clinical scores
for representative colons on day 10 of colitis (see e). Data are
representative of two or three independent experiments. n
represents biologically independent animals. Bars indicate mean ± SEM
values in a-c, e, f.
∗p < 0.05, ∗∗p < 0.01, and
∗∗∗p < 0.001 in one-way (a,
c) or two-way (b, e) analysis of
variance followed by the Bonferroni post hoc test or two-tailed Student’s
t test (f).
"V体育平台登录" Comment in
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Microbiome Modulation of the Host Adaptive Immunity through Bile Acid Modification.Cell Metab. 2020 Mar 3;31(3):445-447. doi: 10.1016/j.cmet.2020.02.006. Cell Metab. 2020. PMID: 32130878
References
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- Ridlon JM, Kang DJ & Hylemon PB Bile salt biotransformations by human intestinal bacteria. Journal of lipid research 47, 241–259, doi:10.1194/jlr.R500013-JLR200 (2006). - DOI (VSports最新版本) - PubMed
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