Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

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Supplementation of Geranylgeraniol and Tocotrienols to High-Fat Diet Shifts the Gut Microbiome Composition and Function in Type 2 Diabetic Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_026 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 393-393

Author(s):

Moamen Elmassry ◽

Eunhee Chung ◽

Abdul Hamood ◽

Chwan-Li Shen

Keyword(s):

Relative Abundance ◽

Gut Microbiome ◽

High Fat Diet ◽

Alpha Diversity ◽

Control Group ◽

Rrna Gene ◽

High Fat ◽

Microbiome Composition ◽

And Function

Abstract Objectives In recent years, characterization of gut microbiota composition and function were linked to the progression of type 2 diabetes mellitus. Recent evidence showed that Geranylgeraniol, an isoprenoid found in fruits, vegetables, and grains, improves glucose homeostasis. Similarly, Tocotrienols, a subfamily of vitamin E, also contains anti-diabetic properties. In this study, we examined the combined effect of geranylgeraniol and tocotrienols on the composition and function of gut microbiome in obese male mice. Methods Forty male C57BL/6J mice were assigned to 4 groups in a factorial design as follows: high-fat diet (HFD) (control group), HFD + geranylgeraniol [400 mg/kg diet] (GG group), HFD + tocotrienols [400 mg/kg diet] (TT group), and HFD + geranylgeraniol + tocotrienols (G + T group) for 14 weeks. 16S rRNA gene sequencing was done from cecal samples and microbiome and data analysis was performed with QIIME2 and PICRUSt2. Results Across all groups, the most abundant phyla were Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. There was no difference in alpha diversity among different groups. Different treatments influenced the relative abundance of certain bacteria. In the Bacteroidetes phylum, the relative abundance of family S24–7 increased in the TT group only. In the Firmicutes phylum, the relative abundance of family Lachnospiraceae was reduced upon the supplementation of geranylgeraniol or tocotrienols; individually or in combination. In Verrucomicrobia phylum, Akkermansia muciniphila relative abundance was reduced in the TT group but increased in the G + T group. The results of functional profiling of the gut microbiome revealed that geranylgeraniol supplementation caused an increase in the proportion of biosynthetic pathways related to purine, pyrimidine, and inosine-5’-phosphate and hexitol fermentation, and a decrease in the proportion of pathways involved in the biosynthesis of isoleucine, valine, histidine, arginine, and chorismate. The G + T group increased pathways related to thiamine diphosphate biosynthesis, and decreased others involved into sulfur oxidation and methylerythritol phosphate. Conclusions The influence of geranylgeraniol and tocotrienols supplementation on gut microbiome composition and function, suggests a prebiotic potential for the potential of geranylgeraniol and tocotrienols. Funding Sources American River Nutrition, LLC, Hadley, MA.

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Modulation of Gut Microbiota by Lonicera caerulea L. Berry Polyphenols in a Mouse Model of Fatty Liver Induced by High Fat Diet

Molecules ◽

10.3390/molecules23123213 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3213 ◽

Cited By ~ 23

Author(s):

Shusong Wu ◽

Ruizhi Hu ◽

Hironobu Nakano ◽

Keyu Chen ◽

Ming Liu ◽

...

Keyword(s):

Mouse Model ◽

Gut Microbiota ◽

Fatty Liver ◽

Relative Abundance ◽

High Fat Diet ◽

Rrna Gene ◽

Protective Effects ◽

High Fat ◽

Lonicera Caerulea ◽

Alcoholic Fatty Liver

Polyphenols from the Lonicera caerulea L. berry have shown protective effects on experimental non-alcoholic fatty liver disease (NAFLD) in our previous studies. As endotoxins from gut bacteria are considered to be the major trigger of inflammation in NAFLD, this study aims to clarify the regulatory effects of L. caerulea L. berry polyphenols (LCBP) on gut microbiota in a high fat diet (HFD)-induced mouse model. C57BL/6N mice were fed with a normal diet, HFD, or HFD containing 0.5–1% of LCBP for 45 days. The results revealed that supplementation with LCBP decreased significantly the levels of IL-2, IL-6, MCP-1, and TNF-α in serum, as well as endotoxin levels in both serum and liver in HFD-fed mice. Fecal microbiota characterization by high throughput 16S rRNA gene sequencing revealed that a HFD increased the Firmicutes/Bacteroidetes ratio, and LCBP reduced this ratio by increasing the relative abundance of Bacteroides, Parabacteroides, and another two undefined bacterial genera belonging to the order of Bacteroidales and family of Rikenellaceae, and also by decreasing the relative abundance of six bacterial genera belonging to the phylum Firmicutes, including Staphylococcus, Lactobacillus, Ruminococcus, and Oscillospira. These data demonstrated that LCBP potentially attenuated inflammation in NAFLD through modulation of gut microbiota, especially the ratio of Firmicutes to Bacteroidetes.

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Conventional myelosuppressive chemotherapy for non-haematological malignancy disrupts the intestinal microbiome

BMC Cancer ◽

10.1186/s12885-021-08296-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lito E. Papanicolas ◽

Sarah K. Sims ◽

Steven L. Taylor ◽

Sophie J. Miller ◽

Christos S. Karapetis ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Haematological Malignancy ◽

Amplicon Sequencing ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Conventional Chemotherapy ◽

Myelosuppressive Chemotherapy ◽

Gram Positive Bacteria ◽

Faecal Samples

Abstract Background The gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown. Methods Faecal samples from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7–12 days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota diversity and composition was determined by 16S rRNA gene amplicon sequencing. Results Compared to pre-chemotherapy samples, samples collected 7–12 days following chemotherapy exhibited increased richness (mean 120 observed species ± SD 38 vs 134 ± 40; p = 0.007) and diversity (Shannon diversity: mean 6.4 ± 0.43 vs 6.6 ± 0.41; p = 0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11]; p = 0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13]; p = 0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03]; p = 0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle. Conclusions Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.

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The Effects of Chinese Medicine QRD, Antibiotics, and Probiotics on Therapy and Gut Microbiota in Septic Rats

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.712028 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huiling Cao ◽

Chunhui Zong ◽

Wenkui Dai ◽

Qiaoying Gao ◽

Donghua Li ◽

...

Keyword(s):

Chinese Medicine ◽

Gut Microbiota ◽

Survival Rates ◽

Amplicon Sequencing ◽

Medical Emergency ◽

Control Group ◽

Rrna Gene ◽

Sham Operation ◽

Therapeutic Effects

Sepsis is a common and often treacherous medical emergency with a high mortality and long-term complications in survivors. Though antibiotic therapy can reduce death rate of sepsis significantly, it impairs gut microbiota (GM), which play imperative roles in human health. In this study, we compared the therapeutic effects of antibiotics, probiotics, and Chinese medicine QRD on the survival rates of septic model and observed the GM characteristics of experimental rats via 16S rRNA gene amplicon sequencing. The 72 h survival rates of septic rat demonstrated the significant therapeutic effects in the three groups treated with antibiotics (AT), Chinses medicine QRD (QT), and probiotics (PT), which were elevated from the survival rate of 26.67% for the sepsis control group (ST) to 100.0% for AT, 88.24% for QT, and 58.33% for PT. The original characteristics of GM identified in the sham operation controls (SC) were relatively similar to those in PT and QT; nevertheless, the AT rats were shown dramatically decreased in the GM diversity. In addition, the septic rats in AT were revealed the higher abundances of Escherichia Shigella, Proteus, Morganella, Enterococcus, and Lysinibacillus, but the lower those of Parabacteroides, Alistipes, Desulfovibrio, Bacteroides, Helicobacter, Mucispirillum, Oscillibacter, Lachnospiraceae, and Ruminiclostridium 9, when compared to the PT and QT rats. By contrast, the GM of PT and QT rats shared similar diversity and structure. Our findings indicated that QRD increased the survival rates without impairment of the GM characteristics, which provides novel insights into the role of Chinese medicine in therapy and long-term recovery of sepsis.

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Effects of gut microbiota on leptin expression and body weight are lessened by high-fat diet in mice

British Journal Of Nutrition ◽

10.1017/s0007114520001117 ◽

2020 ◽

Vol 124 (4) ◽

pp. 396-406 ◽

Cited By ~ 1

Author(s):

Hongyang Yao ◽

Chaonan Fan ◽

Xiuqin Fan ◽

Yuanyuan Lu ◽

Yuanyuan Wang ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

High Fat Diet ◽

Body Weight Gain ◽

High Fat ◽

Hepatic Expression ◽

Reduced Body ◽

Expression Of Genes ◽

Underlying Mechanisms ◽

Leptin Expression

AbstractAberration in leptin expression is one of the most frequent features in the onset and progression of obesity, but the underlying mechanisms are still unclear and need to be clarified. This study investigated the effects of the absence of gut microbiota on body weight and the expression and promoter methylation of the leptin. Male C57 BL/6 J germ-free (GF) and conventional (CV) mice (aged 4–5 weeks) were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for 16 weeks. Six to eight mice from each group, at 15 weeks, were administered exogenous leptin for 7 d. Leptin expression and body weight gain in GF mice were increased by NFD with more CpG sites hypermethylated at the leptin promoter, whereas there was no change with HFD, compared with CV mice. Adipose or hepatic expression of genes associated with fat synthesis (Acc1, Fas and Srebp-1c), hydrolysis and oxidation (Atgl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was lower, and hypothalamus expression of Pomc and Socs3 was higher in GF mice than levels in CV mice, particularly with NFD feeding. Exogenous leptin reduced body weight in both types of mice, with a greater effect on CV mice with NFD. Adipose Lep-R expression was up-regulated, and hepatic Fas and hypothalamic Socs3 were down-regulated in both types of mice. Expression of fat hydrolysis and oxidative genes (Atgl, Hsl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was up-regulated in CV mice. Therefore, the effects of gut microbiota on the leptin expression and body weight were affected by dietary fat intake.

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Preventive Effects of Kaempferol on High-Fat Diet-Induced Obesity Complications in C57BL/6 Mice

BioMed Research International ◽

10.1155/2020/4532482 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Tieqiao Wang ◽

Qiaomin Wu ◽

Tingqi Zhao

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Blood Glucose ◽

Gut Microbiota ◽

Serum Cholesterol ◽

High Fat Diet ◽

Liver Weight ◽

Control Group ◽

High Fat ◽

High Blood Glucose

Kaempferol is a dietary flavanol that regulates cellular lipid and glucose metabolism. Its mechanism of action in preventing hepatic steatosis and obesity-related disorders has yet to be clarified. The purpose of this research was to examine kaempferol’s antiobesity effects in high-fat diet- (HFD-) fed mice and to investigate its impact on their gut microbiota. Using a completely randomized design, 30 mice were equally assigned to a control group, receiving a low-fat diet, an HFD group, receiving a high-fat diet, and an HFD+kaempferol group, receiving a high-fat diet and kaempferol doses of 200 mg/kg in the diet. After eight weeks, the HFD mice displayed substantial body and liver weight gain and high blood glucose and serum cholesterol levels. However, treatment with kaempferol moderated body and liver weight gain and elevation of blood glucose and serum cholesterol and triglyceride levels. Examination of 16S ribosomal RNA showed that HFD mice exhibited decreased microbial diversity, but kaempferol treatment maintained it to nearly the same levels as those in the control group. In conclusion, kaempferol can protect against obesity and insulin resistance in mice on a high-fat diet, partly through regulating their gut microbiota and moderating the decrease in insulin resistance.

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Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet

mBio ◽

10.1128/mbio.00470-17 ◽

2017 ◽

Vol 8 (3) ◽

Cited By ~ 47

Author(s):

Chao Kang ◽

Bin Wang ◽

Kanakaraju Kaliannan ◽

Xiaolan Wang ◽

Hedong Lang ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

High Fat Diet ◽

Rrna Gene ◽

Low Grade ◽

High Fat ◽

Microbial Dysbiosis ◽

Low Grade Inflammation ◽

Metabolic Endotoxemia

ABSTRACT Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation. IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP. Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP.

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A Metabolomic Study on the Intervention of Traditional Chinese Medicine Qushi Huayu Decoction on Rat Model of Fatty Liver Induced by High-Fat Diet

BioMed Research International ◽

10.1155/2019/5920485 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Xiao-jun Gou ◽

Shanshan Gao ◽

Liang Chen ◽

Qin Feng ◽

Yi-yang Hu

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Fatty Liver ◽

Mechanism Of Action ◽

High Fat Diet ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

High Fat ◽

Pattern Recognition Analysis ◽

And Control

Qushi Huayu Decoction (QHD), an important clinically proved herbal formula, has been reported to be effective in treating fatty liver induced by high-fat diet in rats. However, the mechanism of action has not been clarified at the metabolic level. In this study, a urinary metabolomic method based on gas chromatography-mass spectrometry (GC-MS) coupled with pattern recognition analysis was performed in three groups (control, model, and QHD group), to explore the effect of QHD on fatty liver and its mechanism of action. There was obvious separation between the model group and control group, and the QHD group showed a tendency of recovering to the control group in metabolic profiles. Twelve candidate biomarkers were identified and used to explore the possible mechanism. Then, a pathway analysis was performed using MetaboAnalyst 3.0 to illustrate the pathways of therapeutic action of QHD. QHD reversed the urinary metabolite abnormalities (tryptophan, uridine, and phenylalanine, etc.). Fatty liver might be prevented by QHD through regulating the dysfunctions of phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and tryptophan metabolism. This work demonstrated that metabolomics might be helpful for understanding the mechanism of action of traditional Chinese medicine for future clinical evaluation.

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Ampicillin-Improved Glucose Tolerance in Diet-Induced Obese C57BL/6NTac Mice Is Age Dependent

Journal of Diabetes Research ◽

10.1155/2013/319321 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 19

Author(s):

I. Rune ◽

C. H. F. Hansen ◽

M. Ellekilde ◽

D. S. Nielsen ◽

K. Skovgaard ◽

...

Keyword(s):

Dendritic Cell ◽

Tumor Necrosis Factor ◽

Glucose Tolerance ◽

Gut Microbiota ◽

High Fat Diet ◽

Tumor Necrosis ◽

Control Group ◽

High Fat ◽

Amyloid A ◽

Necrosis Factor

Ampicillin has been shown to improve glucose tolerance in mice. We hypothesized that this effect is present only if treatment is initiated prior to weaning and that it disappears when treatment is terminated. High-fat fed C57BL/6NTac mice were divided into groups that received Ampicillin at different ages or not at all. We found that both diet and Ampicillin significantly changed the gut microbiota composition in the animals. Furthermore, there was a significant improvement in glucose tolerance in Ampicillin-treated, five-week-old mice compared to nontreated mice in the control group. At study termination, expressions of mRNA coding for tumor necrosis factor, serum amyloid A, and lactase were upregulated, while the expression of tumor necrosis factor (ligand) superfamily member 15 was downregulated in the ileum of Ampicillin-treated mice. Higher dendritic cell percentages were found systemically in high-fat diet mice, and a lower tolerogenic dendritic cell percentage was found both in relation to high-fat diet and late Ampicillin treatment. The results support our hypothesis that a “window” exists early in life in which an alteration of the gut microbiota affects glucose tolerance as well as development of gut immunity and that this window may disappear after weaning.

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Tiansi Liquid Modulates Gut Microbiota Composition and Tryptophan–Kynurenine Metabolism in Rats with Hydrocortisone-Induced Depression

Molecules ◽

10.3390/molecules23112832 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2832 ◽

Cited By ~ 4

Author(s):

Dan Cheng ◽

Hongsheng Chang ◽

Suya Ma ◽

Jian Guo ◽

Gaimei She ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Performance ◽

Negative Relationship ◽

Treated Group ◽

Control Group ◽

Microbiota Composition ◽

Traditional Chinese Herbal Medicine ◽

Underlying Mechanisms ◽

Gut Microbiota Composition

Tiansi Liquid is a traditional Chinese herbal medicine used to treat depression; however, the underlying mechanisms remain unclear. Here, we examined the effect of Tiansi Liquid in a rat model of hydrocortisone-induced depression using behavioral testing, 16S rRNA high-throughput pyrosequencing and high-performance liquid chromatography-mass spectrometry-based metabolomics of the tryptophan (TRP)–kynurenine (KYN) pathway. Tiansi Liquid significantly improved the sucrose preference and exploratory behavior of the depressive rats. The richness of intestinal mucosa samples from the model (depressive) group tended to be higher than that from the control group, while the richness was higher in the Tiansi Liquid-treated group than in the model group. Tiansi Liquid increased the relative abundance of some microbiota (Ruminococcaceae, Lactococcus, Lactobacillus, Lachnospiraceae_NK4A136_group). Metabolomics showed that Tiansi Liquid reduced the levels of tryptophan 2,3 dioxygenase, indoleamine 2,3-dioxygenase, quinoline and the KYN/TRP ratio, while increasing kynurenic acid and 5-HT levels. Correlation analysis revealed a negative relationship between the relative abundance of the Lachnospiraceae_NK4A136_group and quinoline content. Collectively, these findings suggest that Tiansi Liquid ameliorates depressive symptoms in rats by modulating the gut microbiota composition and metabolites in the TRP–KYN pathway.

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