-
Journal of Diabetes Apr 2024Depression is the most common psychological disorder in patients with type 1 diabetes (T1D). However, the characteristics of microbiota and metabolites in these patients...
BACKGROUND
Depression is the most common psychological disorder in patients with type 1 diabetes (T1D). However, the characteristics of microbiota and metabolites in these patients remain unclear. This study aimed to investigate microbial and metabolomic profiles and identify novel biomarkers for T1D with depression.
METHODS
A case-control study was conducted in a total of 37 T1D patients with depression (TD+), 35 T1D patients without depression (TD-), and 29 healthy controls (HCs). 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis were conducted to investigate the characteristics of microbiota and metabolites. The association between altered microbiota and metabolites was explored by Spearman's rank correlation and visualized by a heatmap. The microbial signatures to discriminate TD+ from TD- were identified by a random forest (RF) classifying model.
RESULTS
In microbiota, 15 genera enriched in TD- and 2 genera enriched in TD+, and in metabolites, 14 differential metabolites (11 upregulated and 3 downregulated) in TD+ versus TD- were identified. Additionally, 5 genera (including Phascolarctobacterium, Butyricimonas, and Alistipes from altered microbiota) demonstrated good diagnostic power (area under the curve [AUC] = 0.73; 95% CI, 0.58-0.87). In the correlation analysis, Butyricimonas was negatively correlated with glutaric acid (r = -0.28, p = 0.015) and malondialdehyde (r = -0.30, p = 0.012). Both Phascolarctobacterium (r = 0.27, p = 0.022) and Alistipes (r = 0.31, p = 0.009) were positively correlated with allopregnanolone.
CONCLUSIONS
T1D patients with depression were characterized by unique profiles of gut microbiota and serum metabolites. Phascolarctobacterium, Butyricimonas, and Alistipes could predict the risk of T1D with depression. These findings provide further evidence that the microbiota-gut-brain axis is involved in T1D with depression.
Topics: Humans; Case-Control Studies; Depression; Diabetes Mellitus, Type 1; RNA, Ribosomal, 16S; Gastrointestinal Microbiome
PubMed: 38599848
DOI: 10.1111/1753-0407.13542 -
Frontiers in Sports and Active Living 2023The gut microbiome plays a fundamental role in host homeostasis through regulating immune functions, enzyme activity, and hormone secretion. Exercise is associated with...
INTRODUCTION
The gut microbiome plays a fundamental role in host homeostasis through regulating immune functions, enzyme activity, and hormone secretion. Exercise is associated with changes in gut microbiome composition and function. However, few studies have investigated the gut microbiome during training periodization. The present study aimed to investigate the relationship between training periodization and the gut microbiome in elite athletes.
METHODS
In total, 84 elite athletes participated in the cross-sectional study; and gut microbiome was determined during their transition or preparation season period. Further, 10 short-track speed skate athletes participated in the longitudinal study, which assessed the gut microbiome and physical fitness such as aerobic capacity and anaerobic power in the general and specific preparation phase of training periodization. The gut microbiome was analyzed using 16S rRNA sequencing.
RESULTS
The cross-sectional study revealed significant differences in and genera and in enterotype distribution between transition and preparation season phase periodization. In the longitudinal study, training phase periodization altered the level of , , and in the microbiome. Such changes in the microbiome were significantly correlated with alternations in aerobic capacity and tended to correlate with the anaerobic power.
DISCUSSION
These findings suggest that periodization alters the gut microbiome abundance related to energy metabolism and trainability of physical fitness. Athlete's condition may thus be mediated to some extent by the microbiota in the intestinal environment.
PubMed: 37521099
DOI: 10.3389/fspor.2023.1219345 -
Gut Microbes 2024Colorectal cancer (CRC), a malignant tumor worldwide, is associated with gut microbiota. The influence of gut microbe-derived metabolites on CRC has attracted a lot of...
Colorectal cancer (CRC), a malignant tumor worldwide, is associated with gut microbiota. The influence of gut microbe-derived metabolites on CRC has attracted a lot of attention. However, the role of immunity mediated by commensal microbiota-derived metabolites in tumorigenesis of CRC is not intensively explored. Here we monitored the gut microbial dysbiosis in CRC mouse model ( model) without dietary and pharmacological intervention, followed by characterized of metabolites enriched in CRC model mice. Profound changes of gut microbiome (bacteriome) were observed during intestinal disorders. Metabolomic profiling indicated that agmatine, derived from the gut bacteria and , could interact with Rnf128 to suppress the Rnf128-mediated ubiquitination of β-catenin to further upregulate the downstream targets of β-catenin including Cyclin D1, Lgr5, CD44 and C-myc, thus activating Wnt signaling. The activated Wnt signaling pathway promoted dysplasia of intestinal cells and inflammatory infiltration of lymphocytes via inducing the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) and downregulation of anti-inflammatory cytokine (IL-10), thereby contributing to colorectal carcinogenesis. Therefore, our study presented novel insights into the roles and mechanisms of gut microbiota in pathogenesis of CRC.
Topics: Animals; Gastrointestinal Microbiome; Colorectal Neoplasms; Mice; Carcinogenesis; Wnt Signaling Pathway; Inflammation; Bacteria; Mice, Inbred C57BL; beta Catenin; Dysbiosis; Humans; Disease Models, Animal; Cytokines; Symbiosis; Male
PubMed: 38706224
DOI: 10.1080/19490976.2024.2348441 -
Microorganisms Dec 2023Ischemic stroke (IS) can be caused by perturbations of the gut-brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk...
Ischemic stroke (IS) can be caused by perturbations of the gut-brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk factors and can influence the brain through the production of different metabolites, such as short-chain fatty acids (SCFAs), indole and derivatives. This study examines ecological changes in the GM and its metabolic activities after stroke. Fecal samples of 10 IS patients were compared to 21 healthy controls (CTRLs). GM ecological profiles were generated via 16S rRNA taxonomy as functional profiles using metabolomics analysis performed with a gas chromatograph coupled to a mass spectrometer (GC-MS). Additionally fecal zonulin, a marker of gut permeability, was measured using an enzyme-linked immuno assay (ELISA). Data were analyzed using univariate and multivariate statistical analyses and correlated with clinical features and biochemical variables using correlation and nonparametric tests. Metabolomic analyses, carried out on a subject subgroup, revealed a high concentration of fecal metabolites, such as SCFAs, in the GM of IS patients, which was corroborated by the enrichment of SCFA-producing bacterial genera such as , Christensellaceae, and . Conversely, indole and 3-methyl indole (skatole) decreased compared to a subset of six CTRLs. This study illustrates how IS might affect the gut microbial milieu and may suggest potential microbial and metabolic biomarkers of IS. Expanded populations of and enrichment of acetic acid could be considered potential disease phenotype signatures.
PubMed: 38257864
DOI: 10.3390/microorganisms12010037 -
Immunity, Inflammation and Disease Aug 2023As a polyphenolic compound originated from the food spice turmeric, curcumin (CUR) has various pharmacological effects, such as anti-inflammatory, antioxidation,...
BACKGROUND
As a polyphenolic compound originated from the food spice turmeric, curcumin (CUR) has various pharmacological effects, such as anti-inflammatory, antioxidation, antiproliferative, and antiangiogenic activities. Psoriasis is centered on the overproduction of Th1- and Th2-related cytokines (e.g., interleukin [IL]-23, IL-17, TNF-α, IL-22), which is involved in the occurrence and development of its pathogenesis. However, whether CUR is involved in the treatment of psoriasis and its specific mechanisms are not fully understood.
METHODS
In this study, we detected the therapeutic effect of CUR (100 mg/kg/day) on IMQ-induced dermatitis in mice, analyzed by PASI scores, ELISA, HE staining, immunofluorescence. Moreover, we further confirmed the alteration in the relative abundance of the gut microbiota through 16sRNA to explore whether CUR could regulate the gut microbiota of IMQ-induced mice.
RESULT
Through intragastric administration, CUR can alleviate psoriasis-like lesions of mice by decreasing PASI scores, reducing the level of IL-6, IL-17A, IL-22, IL-23, TNF-α, and TGF-β1, promoting the expression of IL-10. Moreover, 16sRNA sequencing revealed that CUR could regulate the alteration in the abundance alteration of gut microbiota related to inflammation, such as Alistipes, Mucispirillum, and Rikenella at genus level. The correlation analysis further confirmed the close association between important microflora and psoriasis-like inflammation indicators.
CONCLUSIONS
CUR exerts the effect of alleviating dermatitis of psoriatic mice by regulating Th-17 related inflammatory factors. Moreover, the changes in gut microbiota via CUR may be another factor of relieving IMQ-induced lesions in mice. Therefore, CUR may be a highly promising candidate for the treatment of psoriasis.
Topics: Animals; Mice; Gastrointestinal Microbiome; Curcumin; Imiquimod; Tumor Necrosis Factor-alpha; Inflammation; Interleukin-23; Dermatitis
PubMed: 37647442
DOI: 10.1002/iid3.967 -
Pharmacological Research Sep 2023Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated colorectal cancer (CAC) with poor prognosis. IBD etiology remains...
BACKGROUND
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated colorectal cancer (CAC) with poor prognosis. IBD etiology remains undefined but involves environmental factors, genetic predisposition, microbiota imbalance (dysbiosis) and mucosal immune defects. Mesenchymal stromal cell (MSC) injections have shown good efficacy in reducing intestinal inflammation in animal and human studies. However, their effect on tumor growth in CAC and their capacity to restore gut dysbiosis are not clear.
METHODS
The outcome of systemic administrations of in vitro expanded human intestinal MSCs (iMSCs) on tumor growth in vivo was evaluated using the AOM/DSS model of CAC in C57BL/6J mice. Innate and adaptive immune responses in blood, mesenteric lymph nodes (MLNs) and colonic tissue were analyzed by flow cytometry. Intestinal microbiota composition was evaluated by 16S rRNA amplicon sequencing.
RESULTS
iMSCs significantly inhibited colitis and intestinal tumor development, reducing IL-6 and COX-2 expression, and IL-6/STAT3 and PI3K/Akt signaling. iMSCs decreased colonic immune cell infiltration, and partly restored intestinal monocyte homing and differentiation. iMSC administration increased the numbers of Tregs and IFN-γCD8 T cells in the MLNs while decreasing the IL-4Th2 response. It also ameliorated intestinal dysbiosis in CAC mice, increasing diversity and Bacillota/Bacteroidota ratio, as well as Akkermansia abundance, while reducing Alistipes and Turicibacter, genera associated with inflammation.
CONCLUSION
Administration of iMSCs protects against CAC, ameliorating colitis and partially reverting intestinal dysbiosis, supporting the use of MSCs for the treatment of IBD.
Topics: Humans; Mice; Animals; Colitis-Associated Neoplasms; Interleukin-6; Mice, Inbred C57BL; Dysbiosis; CD8-Positive T-Lymphocytes; RNA, Ribosomal, 16S; Phosphatidylinositol 3-Kinases; Colitis; Inflammation; Colon; Inflammatory Bowel Diseases; Immunity; Mesenchymal Stem Cells; Dextran Sulfate; Disease Models, Animal
PubMed: 37586618
DOI: 10.1016/j.phrs.2023.106891 -
Frontiers in Cellular and Infection... 2023There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a...
BACKGROUND
There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a comprehensive understanding of gut microbiota disturbance in children with GERD through combined metagenomic and metabolomic analysis.
METHODS
30 children with GERD and 30 healthy controls (HCs) were continuously enrolled, and the demographic and clinical characteristics of the subjects were collected. First, 16S rRNA sequencing was used to evaluate differences in the gut microbiota between children with GERD and HC group, and 10 children with GERD and 10 children in the HC group were selected for metagenomic analysis. Nontargeted metabolomic analysis was performed using liquid chromatography/mass spectrometry (LC/MS), and metagenomic and metabolomic data were analyzed together.
RESULTS
There were significant differences in the gut microbiota diversity and composition between children with GERD and HCs. The dominant bacteria in children with GERD were Proteobacteria and Bacteroidota. At the species level, the top three core bacterial groups were , and . The main differential pathways were identified to be related to energy, amino acid, vitamin, carbohydrate and lipid metabolism. LC/MS detected 288 different metabolites in the positive and negative ion modes between children with GERD and HCs, which were mainly involved in arachidonic acid (AA), tyrosine, glutathione and caffeine metabolism.
CONCLUSION
This study provides new evidence of the pathogenesis of GERD. There are significant differences in the gut microbiota, metabolites and metabolic pathways between HCs and children with GERD, and the differences in metabolites are related to specific changes in bacterial abundance. In the future, GERD may be treated by targeting specific bacteria related to AA metabolism.
Topics: Humans; Child; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Metabolomics; Bacteria; Metagenomics; Gastroesophageal Reflux
PubMed: 37900308
DOI: 10.3389/fcimb.2023.1267192 -
Frontiers in Cellular and Infection... 2023Microbiome dysfunction is known to aggravate acute pancreatitis (AP); however, the relationship between this dysfunction and metabolite alterations is not fully...
BACKGROUND AND PURPOSE
Microbiome dysfunction is known to aggravate acute pancreatitis (AP); however, the relationship between this dysfunction and metabolite alterations is not fully understood. This study explored the crosstalk between the microbiome and metabolites in AP mice.
METHODS
Experimental AP models were established by injecting C57/BL mice with seven doses of cerulein and one dose of lipopolysaccharide (LPS). Metagenomics and untargeted metabolomics were used to identify systemic disturbances in the microbiome and metabolites, respectively, during the progression of AP.
RESULTS
The gut microbiome of AP mice primarily included Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, and "core microbiota" characterized by an increase in Proteobacteria and a decrease in Actinobacteria. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that significantly different microbes were involved in several signaling networks. Untargeted metabolomics identified 872 metabolites, of which lipids and lipid-like molecules were the most impacted. An integrated analysis of metagenomics and metabolomics indicated that acetate kinase () gene expression was associated with various gut microbiota, including , , and , and was strongly correlated with the metabolite daphnoretin. The functional gene, -acetyl-L-serine sulfhydrylase (), was associated with , , and , and linked to bufalin and phlorobenzophenone metabolite production.
CONCLUSION
This study identified the relationship between the gut microbiome and metabolite levels during AP, especially the , and -associated functional genes, and . Expression of these genes was significantly correlated to the production of the anti-inflammatory and antitumor metabolites daphnoretin and bufalin.
Topics: Animals; Mice; Metagenomics; Acute Disease; Pancreatitis; Microbiota; Signal Transduction; Bacteroidetes; Lactobacillus
PubMed: 37621874
DOI: 10.3389/fcimb.2023.1134321 -
Frontiers in Microbiology 2023Dysbiosis of gut microbiota and metabolic pathway disorders are closely related to the ulcerative colitis. Through network pharmacology, we found that puerarin is a...
Dysbiosis of gut microbiota and metabolic pathway disorders are closely related to the ulcerative colitis. Through network pharmacology, we found that puerarin is a potential ingredient that can improve the crypt deformation and inflammatory infiltration in mice, and decrease the levels of IL-1β, IL-6 and TNF-α significantly. , and gradually became dominant bacteria in UC mice, which were positively correlated with inflammatory factors. Puerarin effectively improved dysbiosis by reducing the abundance of , and , and increasing the level of . Correlation network and metabolic function prediction analysis of the microbiota showed that they formed a tightly connected network and were widely involved in carbohydrate metabolism and amino acid metabolism. Specifically, we observed significant changes in the tryptophan metabolism pathway in DSS mice, with an increase in the abundance of and involved in tryptophan metabolism. However, this metabolic disorder was alleviated after puerarin treatment, including the reversal of 3-HAA levels and an increase in the abundance of and involved in kynurenine metabolism, as well as a significant increase in the purine metabolite guanosine. In conclusion, our study suggests that puerarin has a good therapeutic effect on UC, which is partially achieved by restoring the composition and abundance of gut microbiota and their metabolism.
PubMed: 37908541
DOI: 10.3389/fmicb.2023.1279029 -
Heliyon Sep 2023This study aims to investigate the changes in gut microbiota and metabolism of patients with chronic kidney disease (CKD) stage 1-2, as well as the potential impact of...
OBJECT
This study aims to investigate the changes in gut microbiota and metabolism of patients with chronic kidney disease (CKD) stage 1-2, as well as the potential impact of hyperuricemia (HUA) on these factors in CKD stage 1-2 patients.
METHODS
In this study, fecal samples were collected from CKD stage 1-2 without HUA patients (CKD-N group), CKD stage 1-2 with HUA patients (CKD-H group), and healthy people controls (HCs group). The samples were then subjected to the microbiome (16S rRNA gene sequencing) and metabolome (liquid chromatography-tandem mass spectrometry) analyses. The multi-omics datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches.
RESULTS
Gut microbial dysbiosis was found in CKD-N and CKD-H patients. At the phylum level, compared to HCs group, decreased but increased in CKD-H group significantly. in CKD-N group was significantly lower than HCs group. At genus level, , , and significantly changed in CKD groups. was significantly lower in CKD-H group than CKD-N group. Moreover, the fecal metabolome of CKD-N and CKD-H altered significantly. d-glutamine and d-glutamate metabolism, arginine and proline metabolism, histidine metabolism, and lysine biosynthesis were down-regulated in the CKD-N group. Phenylalanine metabolism, arginine and proline metabolism, purine metabolism, and beta-alanine metabolism were up-regulated in the CKD-H group. There was a significant difference between the two CKD groups in phenylalanine metabolism. The abundance change of , , , , and had a close correlation with differential metabolites.
CONCLUSION
The gut microbiota and metabolic status undergo significant changes in CKD patients compared to healthy people. Additionally, HUA has been found to impact the gut microbiota of CKD patients, as well as their metabolism. The close association between gut microbiota and metabolites suggests that the former plays a crucial role in metabolism.
PubMed: 37809388
DOI: 10.1016/j.heliyon.2023.e20328