Effect of rhubarb on gut microbiota-host co-metabolism in rats

doi:10.3969/j.issn.1674-8115.2023.08.007

Abstract

Abstract:

Objective ·To study the effect of rhubarb administration on the balance between intestinal flora and the body. Methods ·Wistar rats were randomly divided into 4 groups (n=8), which were given extractions of rhubarb 0.1 g/kg (low dose group), 2.5 g/kg (medium dose group), 4.5 g/kg (high dose group) and normal saline (control group) by intragastric administration for 5 d, and the daily change of fecal water content of rats was observed. Gas chromatography/time of flight mass spectrometry (GC/TOFMS) approach was used to detect the metabolites in serum, colon tissue and fecal of rats on the 5th day of administration. Principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) were used to analyze the differences of metabolites between different dose groups and the control group. The metabolites with statistical significance were obtained by t-test. Results ·The water content of rat feces in the dose group gradually increased with the time and dose after rhubarb administration. Compared with the control group, 28, 18 and 20 differential metabolites were obtained in serum, colon tissue and fecal samples from different dose groups, which showed significant changes (P<0.05) on the 5th day. At the same time, the levels of 17 serum metabolites, 2 colon tissue metabolites, and 10 fecal metabolites altered significantly in a dose-dependent manner. Among these differential metabolites, some gut microbial-host co-metabolites, including neurotransmitters, indoles, and bile acids, were observed to alter significantly after rhubarb administration. The levels of fecal catechol and indole-3-acetic acid increased while the levels of fecal phenylalanine, 4-aminobutyric acid, L-DOPA, and indole-3-propionic acid decreased. Deoxycholic acid level was significantly elevated in colon tissue samples from the high-dose group. Compared with the control group, phenylalanine, tyrosine, and tryptophan levels in serum samples also increased in different dose groups. In addition, the levels of fumaric acid (one of organic acids related to energy metabolism), was down-regulated in fecal samples but up-regulated in colon tissue and serum samples. With the increase of dosage, the level of glutamic acid (one of amino acids) significantly increased in serum samples but gradually decreased in colon tissue samples. Except for 6-phosphogluconic acid, the levels of carbohydrates and lipid metabolites, including fructose, pyruvate, lactic acid, glucose-1-phosphate, D-glycero-1-phosphate docosenic acid, 13-docosenoic acid, 1-monostearoylglycerol, and cholesterol increased in the serum samples, while those of D-glycero-1-phosphate in colon tissue and lactic acid, glucose-1-phosphate, and linolenic acid in fecal samples decreased. Conclusion ·Rhubarb affects brain-gut axis and bile acid metabolism through the gut microbial-host co-metabolism, and further affects the body's energy metabolism, amino acid metabolism, glycometabolism and lipid metabolism.

Key words: rhubarb, gut microbiota, co-metabolism, gas chromatography/time of flight mass spectrometry (GC/TOFMS)

CLC Number:

R285.5

GAO Yu, YIN Shan, PANG Yue, LIANG Wenyi, LIU Yumin. Effect of rhubarb on gut microbiota-host co-metabolism in rats[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(8): 997-1007.

Figures/Tables 5

TrendMD

References 30

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Class	Significant metabolite	Related bacteria ^{[7, 15-17]}	Fc
			Serum			Colon			Fecal
			Fc1	Fc2	Fc3	Fc1	Fc2	Fc3	Fc1	Fc2	Fc3
Metabolites of gut microbial-proteins, peptides and amino acids/gut microbial-host co-metabolism	Catechol	Lactobacillus^{[+ -]} Clostridium^[]							1.09	-1.06	1.42^①
	Phenylpropionic acid		1.01	1.75^①	1.48^①	5.27^①	8.35^①	5.44^①
	2-hydroxyphenylpropionic acid								-2.08^①	-2.33^①	-2.33^①
	L-DOPA								1.10	-1.44^①	-1.30^①
	Phenylalanine		1.12	1.20^①	1.23^①				-1.28	-1.43^①	-1.49^①
	Tyrosine		1.41^①	1.53^①	1.58^①
	4-aminobutyric acid	Clostridium^[]							-1.30	-1.79^①	-1.35
	Ornithine		1.21^①	1.31^①	2.03^①				-2.08^①	-1.85^①	-2.00^①
	Spermidine								1.58^①	2.17^①	2.30^①
	Tryptophan	Escherichia coli^{[+ -]} Bifidobacterium^[+]	1.07	1.41^①	1.46^①
	Indole-3-acetic acid								1.12	2.06^①	1.92^①
	Indole-3-propionic acid								1.00	-1.10	-2.00^①
	Indole-3-lactic acid		1.08	1.36^①	1.43^①
	Kynurenic acid					1.29^①	1.44^①	-7.14^①
	Xanthuric acid								-1.09	-1.25^①	-1.47^①
	Nicotinic acid					-1.11	-1.11	2.85^①	-1.12	-1.25^①	-1.28^①
	Deoxycholic acid	Lactobacillus^{[+ -]} Bifidobacterium^[+] Bacteroides^[+] Escherichia coli^{[+ -]} Clostridium^[]				-1.03	1.04	2.88^①
	Cholesterol		1.75^①	1.84^①	2.46^①	-1.85	-4.17^①	-3.85^①
	Isoleucine		1.18	1.18	1.22^①				-1.26	-1.28^①	-1.39^①
	Leucine		1.15	1.19	1.24^①				-1.17	-1.25^①	-1.26^①
	Valine		1.21	1.19	1.26^①				-1.21	-1.58^①	-1.67^①
	Isovaleric acid					1.28	1.02	-2.94^①
	Caproic acid					1.04	4.37^①	4.30^①
TCA cycle	Fumaric acid	Bifidobacterium^[+] Lactobacillus^{[+ -]}	2.29^①	2.84^①	3.83^①	1.73^①	1.28	1.25^①	-1.85^①	-1.79^①	-1.75^①
	Malic acid		1.60^①	2.28^①	3.49^①	1.71^①	-1.06^①	1.00	-1.64^①	-2.17^①	-2.04^①
	α-ketoglutaric acid		1.33	1.34	1.60^①
	Citric acid		1.48^①	1.41^①	1.74^①
	Isocitrate		1.53	1.64^①	1.77^①
TCA cycle-amino acid	Glutamic acid		1.27^①	1.31^①	1.43^①				-1.23	-1.61^①	-1.72^①
	Glutamine		2.15^①	2.37^①	3.08^①
	Aspartic acid		1.31^①	1.46^①	1.60^①
	Asparagine		1.17	1.59^①	1.40^①
TCA cycle-glycometabolism	Pyruvate	Bifidobacterium^[+] Bacteroides^[+] Lactobacillus^{[+ -]}	1.09	1.37	1.67^①	-1.03	1.47	2.48^①
	Lactic acid		1.16	1.46^①	1.46^①	1.55^①	-1.07	-1.05	-3.52^①	-2.68^①	-1.05^①
	Fructose		1.08	1.23^①	1.41^①	1.46^①	2.20^①	3.41^①
	6-phosphogluconic acid		-1.09^①	-1.10^①	-1.33^①	1.34^①	1.55^①	-10.00^①
	D-glycero-1-phosphate		1.45	1.95^①	2.03^①	-1.35^①	-1.37	-1.69^①
	Glucose-1-phosphate		1.05	0.85	1.42^①	1.31	1.22	-2.63^①	-1.25^①	-1.29^①	-1.31^①
	β-glycerophosphate					-1.33^①	1.00	-1.56^①
	Ethanolamine phosphate					1.21	-1.67	-1.96^①
	Phosphoenolpyruvate					1.54^①	1.32	-1.56^①
TCA cycle-lipid metabolism	Linolenic acid	Bifidobacterium^[+] Lactobacillus^[+-]							1.04	-1.53^①	-1.52^①
	Docosanoic acid		1.32	3.29^①	1.92^①
	13-docosenoic acid		1.43	1.80^①	2.27^①
	1-monostearoylglycerol		-1.30	1.01	1.53^①

Class	Significant metabolite	Related bacteria ^{[7, 15-17]}	Fc
			Serum			Colon			Fecal
			Fc1	Fc2	Fc3	Fc1	Fc2	Fc3	Fc1	Fc2	Fc3
Metabolites of gut microbial-proteins, peptides and amino acids/gut microbial-host co-metabolism	Catechol	Lactobacillus^{[+ -]} Clostridium^[]							1.09	-1.06	1.42^①
	Phenylpropionic acid		1.01	1.75^①	1.48^①	5.27^①	8.35^①	5.44^①
	2-hydroxyphenylpropionic acid								-2.08^①	-2.33^①	-2.33^①
	L-DOPA								1.10	-1.44^①	-1.30^①
	Phenylalanine		1.12	1.20^①	1.23^①				-1.28	-1.43^①	-1.49^①
	Tyrosine		1.41^①	1.53^①	1.58^①
	4-aminobutyric acid	Clostridium^[]							-1.30	-1.79^①	-1.35
	Ornithine		1.21^①	1.31^①	2.03^①				-2.08^①	-1.85^①	-2.00^①
	Spermidine								1.58^①	2.17^①	2.30^①
	Tryptophan	Escherichia coli^{[+ -]} Bifidobacterium^[+]	1.07	1.41^①	1.46^①
	Indole-3-acetic acid								1.12	2.06^①	1.92^①
	Indole-3-propionic acid								1.00	-1.10	-2.00^①
	Indole-3-lactic acid		1.08	1.36^①	1.43^①
	Kynurenic acid					1.29^①	1.44^①	-7.14^①
	Xanthuric acid								-1.09	-1.25^①	-1.47^①
	Nicotinic acid					-1.11	-1.11	2.85^①	-1.12	-1.25^①	-1.28^①
	Deoxycholic acid	Lactobacillus^{[+ -]} Bifidobacterium^[+] Bacteroides^[+] Escherichia coli^{[+ -]} Clostridium^[]				-1.03	1.04	2.88^①
	Cholesterol		1.75^①	1.84^①	2.46^①	-1.85	-4.17^①	-3.85^①
	Isoleucine		1.18	1.18	1.22^①				-1.26	-1.28^①	-1.39^①
	Leucine		1.15	1.19	1.24^①				-1.17	-1.25^①	-1.26^①
	Valine		1.21	1.19	1.26^①				-1.21	-1.58^①	-1.67^①
	Isovaleric acid					1.28	1.02	-2.94^①
	Caproic acid					1.04	4.37^①	4.30^①
TCA cycle	Fumaric acid	Bifidobacterium^[+] Lactobacillus^{[+ -]}	2.29^①	2.84^①	3.83^①	1.73^①	1.28	1.25^①	-1.85^①	-1.79^①	-1.75^①
	Malic acid		1.60^①	2.28^①	3.49^①	1.71^①	-1.06^①	1.00	-1.64^①	-2.17^①	-2.04^①
	α-ketoglutaric acid		1.33	1.34	1.60^①
	Citric acid		1.48^①	1.41^①	1.74^①
	Isocitrate		1.53	1.64^①	1.77^①
TCA cycle-amino acid	Glutamic acid		1.27^①	1.31^①	1.43^①				-1.23	-1.61^①	-1.72^①
	Glutamine		2.15^①	2.37^①	3.08^①
	Aspartic acid		1.31^①	1.46^①	1.60^①
	Asparagine		1.17	1.59^①	1.40^①
TCA cycle-glycometabolism	Pyruvate	Bifidobacterium^[+] Bacteroides^[+] Lactobacillus^{[+ -]}	1.09	1.37	1.67^①	-1.03	1.47	2.48^①
	Lactic acid		1.16	1.46^①	1.46^①	1.55^①	-1.07	-1.05	-3.52^①	-2.68^①	-1.05^①
	Fructose		1.08	1.23^①	1.41^①	1.46^①	2.20^①	3.41^①
	6-phosphogluconic acid		-1.09^①	-1.10^①	-1.33^①	1.34^①	1.55^①	-10.00^①
	D-glycero-1-phosphate		1.45	1.95^①	2.03^①	-1.35^①	-1.37	-1.69^①
	Glucose-1-phosphate		1.05	0.85	1.42^①	1.31	1.22	-2.63^①	-1.25^①	-1.29^①	-1.31^①
	β-glycerophosphate					-1.33^①	1.00	-1.56^①
	Ethanolamine phosphate					1.21	-1.67	-1.96^①
	Phosphoenolpyruvate					1.54^①	1.32	-1.56^①
TCA cycle-lipid metabolism	Linolenic acid	Bifidobacterium^[+] Lactobacillus^[+-]							1.04	-1.53^①	-1.52^①
	Docosanoic acid		1.32	3.29^①	1.92^①
	13-docosenoic acid		1.43	1.80^①	2.27^①
	1-monostearoylglycerol		-1.30	1.01	1.53^①

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