-
American Journal of Transplantation :... Feb 2023Intestinal commensals can exert immunomodulatory effects on the host, with beneficial or detrimental consequences depending on underlying diseases. We have previously...
Intestinal commensals can exert immunomodulatory effects on the host, with beneficial or detrimental consequences depending on underlying diseases. We have previously correlated longer survival of minor mismatched skin grafts in mice with the presence of an intestinal commensal bacterium, Alistipes onderdonkii. In this study, we investigated its sufficiency and mechanism of action. Oral administration of A onderdonkii strain DSM19147 but not DSM108265 was sufficient to prolong minor mismatched skin graft survival through inhibition of tumor necrosis factor production. Through metabolomic and metagenomic comparisons between DSM19147 and DSM108265, we identified candidate gene products associated with the anti-inflammatory effect of DSM19147. A onderdonkii DSM19147 can lower inflammation both at a steady state and after transplantation and may serve as an anti-inflammatory probiotic beneficial for transplant recipients.
Topics: Animals; Mice; Administration, Oral; Allografts; Graft Rejection; Graft Survival; Mice, Inbred BALB C; Mice, Inbred C57BL; Skin Transplantation; Transplantation, Homologous; Bacteroidetes; Probiotics
PubMed: 36804134
DOI: 10.1016/j.ajt.2022.11.011 -
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 -
Clinical Proteomics Feb 2023Inflammatory bowel disease (IBD) encompasses a group of chronic relapsing disorders which include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD...
BACKGROUND
Inflammatory bowel disease (IBD) encompasses a group of chronic relapsing disorders which include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD and overweight/obesity are increasing in parallel. Here, we investigated alterations in proteomic in serum and metaproteomic in feces of IBD patients with overweight/obesity and aimed to explore the effect of overweight/ obesity on IBD and the underlying mechanism.
METHODS
This prospective observational study (n = 64) comprised 26 health control subjects (HC, 13 with overweight/obesity) and 38 IBD patients (19 with overweight/obesity) at a tertiary hospital. Overweight/obesity was evaluated by body mass index (BMI) and defined as a BMI greater than 24 kg/m. The comprehensive serum proteomic and fecal metaproteomic analyses were conducted by ultra-performance liquid chromatography-Orbitrap Exploris 480 mass spectrometry.
RESULTS
UC and CD presented similar serum molecular profiles but distinct gut microbiota. UC and CD serum exhibited higher levels of cytoskeleton organization- associated and inflammatory response-related proteins than the HC serum. Compared the serum proteome of UC and CD without overweight/obesity, inflammatory response-associated proteins were dramatically decreased in UC and CD with overweight/obesity. Fecal metaproteome identified 66 species in the feces. Among them, Parasutterella excrementihominis was increased in CD compared with that in HC. UC group had a significant enrichment of Moniliophthora roreri, but had dramatically decreased abundances of Alistipes indistinctus, Clostridium methylpentosum, Bacteroides vulgatus, and Schizochytrium aggregatum. In addition, overweight/obesity could improve the microbial diversity of UC. Specifically, the UC patients with overweight/obesity had increased abundance of some probiotics in contrast to those without overweight/obesity, including Parabacteroides distasonis, Alistipes indistincus, and Ruminococcus bromii.
CONCLUSION
This study provided high-quality multi-omics data of IBD serum and fecal samples, which enabled deciphering the molecular bases of clinical phenotypes of IBD, revealing the impacts of microbiota on IBD, and emphasizing the important role of overweight/obesity in IBD.
PubMed: 36759757
DOI: 10.1186/s12014-023-09396-y -
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 Psychiatry 2023Females in the perimenopausal period are susceptible to mood disorders. Perimenopausal panic disorder (PPD) is characterized by repeated and unpredictable panic attacks...
INTRODUCTION
Females in the perimenopausal period are susceptible to mood disorders. Perimenopausal panic disorder (PPD) is characterized by repeated and unpredictable panic attacks during perimenopause, and it impacts the patient's physical and mental health and social function. Pharmacotherapy is limited in the clinic, and its pathological mechanism is unclear. Recent studies have demonstrated that gut microbiota is strongly linked to emotion; however, the relation between PPD and microbiota is limitedly known.
METHODS
This study aimed to discover specific microbiota in PPD patients and the intrinsic connection between them. Gut microbiota was analyzed in PPD patients ( = 40) and healthy controls ( = 40) by 16S rRNA sequencing.
RESULTS
The results showed reduced α-diversity (richness) in the gut microbiota of PPD patients. β-diversity indicated that PPD and healthy controls had different intestinal microbiota compositions. At the genus level, 30 species of microbiota abundance had significantly different between the PPD and healthy controls. In addition, HAMA, PDSS, and PASS scales were collected in two groups. It was found that Bacteroides and Alistipes were positively correlated with PASS, PDSS, and HAMA.
DISCUSSION
Bacteroides and Alistipes dysbiosis dominate imbalanced microbiota in PPD patients. This microbial alteration may be a potential pathogenesis and physio-pathological feature of PPD. The distinct gut microbiota can be a potential diagnostic marker and a new therapeutic target for PPD.
PubMed: 37304433
DOI: 10.3389/fpsyt.2023.1139992 -
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 -
Frontiers in Nutrition 2022The purpose of this experiment was to investigate the effects of different starch and protein levels on lipid metabolism and gut microbes in mice of different genders. A...
The purpose of this experiment was to investigate the effects of different starch and protein levels on lipid metabolism and gut microbes in mice of different genders. A total of 160 male mice were randomly assigned to sixteen groups and fed a 4 × 4 Latin square design with dietary protein concentrations of 16, 18, 20, and 22%, and starch concentrations of 50, 52, 54, and 56%, respectively. The results of the study showed that different proportions of starch and protein had obvious effects on the liver index of mice, and there was a significant interaction between starch and protein on the liver index ( = 0.005). Compared with other protein ratio diets, 18% protein diet significantly increased the serum TBA concentration of mice ( < 0.001), and different starch ratio diets had no effect on serum TBA concentration ( = 0.442). It was proved from the results of ileal tissue HE staining that the low protein diet and the low starch diet were more favorable. There was a significant interaction between diets with different starch and protein levels on , and abundance in feces of mice ( < 0.001). Compared with 16 and 18% protein ratio diets, both 20 and 22% protein diets significantly decreased the and abundance in feces of mice ( < 0.05), and 52% starch ratio diet significantly decreased the and abundance than 50% starch ratio diet of mice ( < 0.05). There was a significant interaction between diets with different starch and protein levels on ( = 0.014) and ( = 0.001) abundance in feces of mice. Taken together, our results suggest that a low protein and starch diet can alter lipid metabolism and gut microbes in mice.
PubMed: 36466418
DOI: 10.3389/fnut.2022.1018026 -
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