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International Journal of Molecular... May 2024The role of the gut microbiota and its interplay with host metabolic health, particularly in the context of type 2 diabetes mellitus (T2DM) management, is garnering... (Comparative Study)
Comparative Study
The role of the gut microbiota and its interplay with host metabolic health, particularly in the context of type 2 diabetes mellitus (T2DM) management, is garnering increasing attention. Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, constitute a class of drugs extensively used in T2DM treatment. However, their potential interactions with gut microbiota remain poorly understood. In this study, we employed computational methodologies to investigate the binding affinities of various gliptins to DPP4-like homologs produced by intestinal bacteria. The 3D structures of DPP4 homologs from gut microbiota species, including , , , , and sp., were predicted using computational modeling techniques. Subsequently, molecular dynamics simulations were conducted for 200 ns to ensure the stability of the predicted structures. Stable structures were then utilized to predict the binding interactions with known gliptins through molecular docking algorithms. Our results revealed binding similarities of gliptins toward bacterial DPP4 homologs compared to human DPP4. Specifically, certain gliptins exhibited similar binding scores to bacterial DPP4 homologs as they did with human DPP4, suggesting a potential interaction of these drugs with gut microbiota. These findings could help in understanding the interplay between gliptins and gut microbiota DPP4 homologs, considering the intricate relationship between the host metabolism and microbial communities in the gut.
Topics: Dipeptidyl Peptidase 4; Diabetes Mellitus, Type 2; Humans; Dipeptidyl-Peptidase IV Inhibitors; Molecular Dynamics Simulation; Gastrointestinal Microbiome; Molecular Docking Simulation; Protein Binding; Bacteria; Bacterial Proteins; Binding Sites
PubMed: 38891933
DOI: 10.3390/ijms25115744 -
Aging Jun 2024Acute pancreatitis (AP) is a prevalent acute abdominal condition, and AP induced colonic barrier dysfunction is commonly observed. Total flavonoids of (TFC) have...
BACKGROUND
Acute pancreatitis (AP) is a prevalent acute abdominal condition, and AP induced colonic barrier dysfunction is commonly observed. Total flavonoids of (TFC) have exhibited noteworthy anti-inflammatory and anti-apoptotic properties.
METHODS
We established AP models, both in animals and cell cultures, employing Cerulein. 16S rRNA gene sequencing was performed to investigate the gut microorganisms changes.
RESULTS
, TFC demonstrated a remarkable capacity to ameliorate AP, as indicated by the inhibition of serum amylase, myeloperoxidase (MPO) levels, and the reduction in pancreatic tissue water content. Furthermore, TFC effectively curtailed the heightened inflammatory response. The dysfunction of colonic barrier induced by AP was suppressed by TFC. At the level, TFC treatment resulted in attenuation of increased cell apoptosis, and regulation of apoptosis related proteins expression in AR42J cells. The increase of , , , and by AP, and decrease of of , , by AP were both reversed by TFC treatment.
CONCLUSIONS
TFC can effectively suppress AP progression and AP induced colonic barrier dysfunction by mitigating elevated serum amylase, MPO levels, water content in pancreatic tissue, as well as curtailing inflammation, apoptosis. The findings presented herein shed light on the potential mechanisms by which TFC inhibit the development of AP progression and AP induced colonic barrier dysfunction.
Topics: Animals; Gastrointestinal Microbiome; Chrysanthemum; Pancreatitis; Flavonoids; Male; Rats; Colon; Apoptosis; Disease Models, Animal; Cell Line; Intestinal Mucosa
PubMed: 38862253
DOI: 10.18632/aging.205924 -
Cancers Apr 2024The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies...
The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder ( = 28) and non-responder ( = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of and was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.
PubMed: 38730627
DOI: 10.3390/cancers16091675 -
Gut Microbes 2024Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify...
Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.
Topics: Animals; Mice; Humans; Colitis, Ulcerative; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Colitis; Machine Learning
PubMed: 38563656
DOI: 10.1080/19490976.2024.2336877 -
Journal of the Science of Food and... Mar 2024Because of their diverse biological activities, polysaccharides derived from Tremella fuciformis have received growing attention. This study aimed to investigate the...
BACKGROUND
Because of their diverse biological activities, polysaccharides derived from Tremella fuciformis have received growing attention. This study aimed to investigate the structural characterization of a purified polysaccharide (designated as PTP-3a) derived from T. fuciformis and explore its interaction with gut microbiota in vitro.
RESULTS
The findings revealed that PTP-3a had a molecular weight of 1.22 × 10 kDa and consisted of fucose, glucose, xylose, mannose and glucuronic acid in a molar ratio of 0.271:0.016:0.275:0.400:0.038. The primary linkage types identified in PTP-3a were 1,3-linked-manp, 1,4-linked-xylp and 1,2,3-linked-fucp, with corresponding ratios of 0.215:0.161:0.15. In addition, PTP-3a demonstrated notable thermal stability and exhibited a triple-helical structure. Moreover, following in vitro fermentation for 48 h, PTP-3a was efficiently utilized, resulting in a reduction in carbohydrate levels, the production of short-chain fatty acids (SCFAs) and pH adjustment. Furthermore, during in vitro fecal microbial fermentation, PTP-3a decreased the relative abundance of Firmicutes while increasing the proportions of Bacteroidetes and Proteobacteria, resulting in a significantly reduced Firmicutes/Bacteroidetes ratio. Additionally, PTP-3a stimulated the growth of beneficial bacteria such as Parabacteroides merdae, Gordonibacter pamelaeae, Bifidobacterium pseudolongum and Parabacteroides distasonis. Importantly, a strong correlation was observed between the production of SCFAs and specific microorganisms.
CONCLUSION
These findings suggested that PTP-3a has potential as a prebiotic for modulating the gut microbiota. © 2024 Society of Chemical Industry.
PubMed: 38520258
DOI: 10.1002/jsfa.13479 -
Microbiological Research Jun 2024As the most abundant gram-negative bacterial order in the gastrointestinal tract, Bacteroidales bacteria have been extensively studied for their contribution to various...
As the most abundant gram-negative bacterial order in the gastrointestinal tract, Bacteroidales bacteria have been extensively studied for their contribution to various aspects of gut health. These bacteria are renowned for their involvement in immunomodulation and their remarkable capacity to break down complex carbohydrates and fibers. However, the human gut microbiota is known to produce many metabolites that ultimately mediate important microbe-host and microbe-microbe interactions. To gain further insights into the metabolites produced by the gut commensal strains of this order, we examined the metabolite composition of their bacterial cell cultures in the stationary phase. Based on their abundance in the gastrointestinal tract and their relevance in health and disease, we selected a total of six bacterial strains from the relevant genera Bacteroides, Phocaeicola, Parabacteroides, and Segatella. We grew these strains in modified Gifu anaerobic medium (mGAM) supplemented with mucin, which resembles the gut microbiota's natural environment. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolite profiling revealed 179 annotated metabolites that had significantly differential abundances between the studied bacterial strains and the control growth medium. Most of them belonged to classes such as amino acids and derivatives, organic acids, and nucleot(s)ides. Of particular interest, Segatella copri DSM 18205 (previously referred to as Prevotella copri) produced substantial quantities of the bioactive metabolites phenylethylamine, tyramine, tryptamine, and ornithine. Parabacteroides merdae CL03T12C32 stood out due to its ability to produce cadaverine, histamine, acetylputrescine, and deoxycarnitine. In addition, we found that strains of the genera Bacteroides, Phocaeicola, and Parabacteroides accumulated considerable amounts of proline-hydroxyproline, a collagen-derived bioactive dipeptide. Collectively, these findings offer a more detailed comprehension of the metabolic potential of these Bacteroidales strains, contributing to a better understanding of their role within the human gut microbiome in health and disease.
Topics: Humans; Chromatography, Liquid; Liquid Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Bacteria; Gastrointestinal Microbiome
PubMed: 38518452
DOI: 10.1016/j.micres.2024.127700 -
Cancers Oct 2023Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in...
Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with and were elevated in mucosa from polyp patients, while ASVs associated with , , and were relatively decreased. Only was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche.
PubMed: 37894412
DOI: 10.3390/cancers15205045 -
Frontiers in Nutrition 2023The aim of the study was to evaluate the effects of Active or Sedentary lifestyle on saliva microbiota composition in Italian schoolchildren.
UNLABELLED
The aim of the study was to evaluate the effects of Active or Sedentary lifestyle on saliva microbiota composition in Italian schoolchildren.
METHODS
Male (114) and female children (8-10 years) belonging to five primary schools in the neighborhoods of Turin were classified as active (A) or sedentary (S) based on PAQ-C-It questionnaire. PCR amplification of salivary DNA targeted the hypervariable V3-V4 regions of the 16S rRNA bacterial genes. DADA2 workflow was used to infer the Amplicon Sequence Variants and the taxonomic assignments; the beta-diversity was obtained by PCoA with the UniFrac method; LEfSe algorithm, threshold at 5%, and Log LDA cutoff at ±0.5 were used to identify differently abundant species in A compared to S saliva sample. Daily food intake was assessed by 3-Days food record. The metabolic potential of microbial communities was assessed by PICRUSt.
RESULTS
No significant differences were found in individual's gender distribution ( = 0.411), anthropometry, BMI ( > 0.05), and all diet composition between A and S groups ( > 0.05). Eight species were differently abundant: (LDA score = -3.76; FDR = 1.5×10-03), (LDA score = -3.17; FDR = 7.45×10-03), (LDA score = -2.96; FDR = 2.76×10-05), (LDA score = -2.43; FDR = 1.3×10-02) are enriched in the A group; , (LDA score = -3.9; FDR = 5.27×10-04), (LDA score = 4.23; FDR = 1.93×10-02), (LDA score = 4.43; FDR = 1.31×10-02; LDA score = 2.94; FDR = 7.45×10-03) are enriched in the S group. A prevalence of superpathway of fatty acid biosynthesis initiation () and catechol degradation II (meta-cleavage pathway) was found in saliva from A compared to S children.
CONCLUSION
Our results showed that active children had an enrichment of species and genera mainly associated with a healthier profile. By contrast, the genera and the species enriched in the sedentary group could be linked to human diseases.
PubMed: 37671197
DOI: 10.3389/fnut.2023.1226891 -
Food & Function Sep 2023Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by dysregulation of lipid metabolism, insulin resistance, and gut microbiota disorder....
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by dysregulation of lipid metabolism, insulin resistance, and gut microbiota disorder. Compared to drug interventions, probiotic interventions may have a more enduring effect without producing any side effects. Thus, the potential of probiotics as a therapeutic approach for diabetes and other metabolic disorders has gained increasing attention in recent years. In this study, we evaluated the therapeutic efficacy of CKCC1913, a potential probiotic strain, in high-fat diet-induced insulin-resistant diabetes using the C57BL/6J mouse animal model. From the results, CKCC1913 has been shown to increase glucose tolerance, reduce fasting blood glucose levels in diabetic mice, and reduce the expression of pro-inflammatory cytokines, such as TNF-α and IL-6. Besides, CKCC1913 intervention effectively alleviated oxidative stress damage by increasing SOD activity, decreasing MDA levels, reducing insulin resistance, and improving dyslipidemia caused by diabetes. The potential mechanism of CKCC1913 in improving metabolic health and alleviating diabetes involves an increased abundance of beneficial bacteria, such as , which directly produce short-chain fatty acids that help regulate immune cells and reduce inflammation. SCFAs also enter the bloodstream and promote antioxidant enzyme activity in the liver, protecting against oxidative damage. Additionally, CKCC1913 influences local bacterial metabolism pathways, such as the superpathway of unsaturated fatty acid biosynthesis, leading to an increase in unsaturated fatty acids, increasing high-density lipoprotein cholesterol (HDL-C) levels and improving lipid metabolism and glucose control in diabetic mice. In summary, in this study, CKCC1913 and its potential impact on metabolic health highlight the promising potential of probiotics as a therapeutic approach for diabetes. Future research should focus on identifying the optimal dose and duration, investigating the long-term effects and mechanisms of action, and exploring the potential use of probiotics as an adjunct to other therapies or in preventing metabolic disorders.
Topics: Animals; Mice; Mice, Inbred C57BL; Diabetes Mellitus, Type 2; Lactobacillus gasseri; Insulin Resistance; Diabetes Mellitus, Experimental; Liver; Antioxidants
PubMed: 37655696
DOI: 10.1039/d3fo01701j -
Acta Neuropsychiatrica Dec 2023The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes ., 2008). The...
Adverse childhood experiences and reoccurrence of illness impact the gut microbiome, which affects suicidal behaviours and the phenome of major depression: towards enterotypic phenotypes.
The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes ., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours (SB) and cognitive deficits; the effects of adverse childhood experiences (ACEs) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc). We determined isometric log-ratio abundances or prevalences of gut microbiome phyla, genera, and species by analysing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing. Six microbiome taxa accounted for 36% of the variance in the depression phenome, namely and (positive associations) and , and (inverse association). This profile (labelled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to SB. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (, and a were positively associated, while and were negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current SB. In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and SB and possibly for the prevention of future episodes.
Topics: Humans; Depressive Disorder, Major; Gastrointestinal Microbiome; Depression; Feces; Adverse Childhood Experiences; Suicidal Ideation; Phenotype
PubMed: 37052305
DOI: 10.1017/neu.2023.21