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Diabetes, Metabolic Syndrome and... 2024( is a gram-positive anaerobe commonly resides in the human gut microbiota. The advent of metagenomics has linked with various diseases, including inflammatory bowel... (Review)
Review
( is a gram-positive anaerobe commonly resides in the human gut microbiota. The advent of metagenomics has linked with various diseases, including inflammatory bowel disease (IBD), obesity, and diabetes mellitus (DM), which has become a growing area of investigation. The initial focus of research primarily centered on assessing the abundance of and its potential association with disease presentation, taking into account variations in sample size, sequencing and analysis methods. However, recent investigations have shifted towards elucidating the underlying mechanistic pathways through which may contribute to disease manifestation. In this comprehensive review, we aim to provide an updated synthesis of the current literature on in the context of IBD, obesity, and DM. We critically analyze relevant studies and summarize the potential molecular mediators implicated in the association between and these diseases. Across numerous studies, various molecules such as methylation-controlled J (MCJ), glucopolysaccharides, ursodeoxycholic acid (UDCA), interleukin(IL)-10, IL-17, and capric acid have been proposed as potential contributors to the link between and IBD. Similarly, in the realm of obesity, molecules such as hydrogen peroxide, butyrate, and UDCA have been suggested as potential mediators, while glycine ursodeoxycholic acid (GUDCA) has been implicated in the connection between and DM. Furthermore, it is imperative to emphasize the necessity for additional studies to evaluate the potential efficacy of targeting pathways associated with as a viable strategy for managing these diseases. These findings have significantly expanded our understanding of the functional role of in the context of IBD, obesity, and DM. This review aims to offer updated insights into the role and potential mechanisms of , as well as potential strategies for the treatment of these diseases.
PubMed: 38496006
DOI: 10.2147/DMSO.S456173 -
Frontiers in Endocrinology 2024This study sought to elucidate the causal association between gut microbiota (GM) composition and type 2 diabetes mellitus (T2DM) through a comprehensive two-sample...
OBJECTIVE
This study sought to elucidate the causal association between gut microbiota (GM) composition and type 2 diabetes mellitus (T2DM) through a comprehensive two-sample bidirectional Mendelian randomization analysis.
METHOD
T2DM data were sourced from the IEU OpenGWAS Project database, complemented by 211 gut microbiota (GM) datasets from the MiBioGen Federation. The primary analytical approach employed was inverse variance weighted (IVW), supplemented by MR-Egger regression and weighted median (WME) methods to investigate their potential interplay. Results were assessed using odds ratios () and 95% confidence intervals (). The robustness and reliability of the findings were confirmed through leave-one-out analysis, heterogeneity testing, and assessment of horizontal pleiotropy. Furthermore, we explored the potential mediating role of metabolites in the pathway linking GM to T2DM.
RESULT
A set of 11 Single Nucleotide Polymorphisms (SNPs) linked to GM were identified as instrumental variables (IVs). The IVW analysis revealed that increased abundance of the , and corresponded to a heightened risk of T2DM. Conversely, higher levels of , and were associated with a reduced risk of T2DM. However, following false discovery rate (FDR) correction, only the abundance of genus Lachnoclostridium retained a significant positive correlation with T2DM risk ( = 1.22, = 0.09), while the other ten GM showed suggestive associations with T2DM. Reverse MR analysis did not reveal any causal relationship between T2DM and the increased risk associated with the identified GM. Additionally, metabolites did not exhibit mediating effects in this context.
CONCLUSION
This study effectively pinpointed specific GM associated with T2DM, potentially paving the way for novel biomarkers in the prevention and treatment of this condition. The findings suggested that probiotics could emerge as a promising avenue for managing T2DM in the future. Furthermore, the analysis indicated that metabolites do not appear to act as mediators in the pathway from GM to T2DM.
Topics: Humans; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Mendelian Randomization Analysis; Reproducibility of Results; Databases, Factual
PubMed: 38495787
DOI: 10.3389/fendo.2024.1313651 -
International Immunopharmacology Apr 2024Dupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively...
BACKGROUND
Dupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively contributing to clinical improvement in patients with atopic dermatitis (AD). As the second genome of human body, growing evidence suggests that the gut microbiome might relate to the host response to treatments. Little is known about the association between dupilumab treatment and gut microbiome in AD patients.
OBJECTIVE
We aimed to characterize the gut microbiome among Chinese subjects with or without AD and determine the potential effect of dupilumab on the gut microbiome.
RESULTS
The 16 s rRNA gene sequencing was conducted on 48 healthy controls (HC), 44 AD patients and 27 AD patients who received dupilumab for 16 weeks. Prior to treatment, we identified the changed beta-diversity, increased Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium and expanded Faecalibacterium among the AD patients compared to HC. After 16 weeks of dupilumab treatment, gut microbiome dysbiosis of the AD patients improved with reversed beta-diversity, closer bacterial connections, increased colonization of Bifidobacterium, Ruminococcus gnavus, and Coprococcus, which were negatively correlated with disease severity indicators. This shift was largely independent of the degree of clinical improvement. Bacterial function analysis revealed further metabolic alterations following dupilumab treatment, including up-regulated expression of genes involved in the indole pathway of tryptophan metabolism, corroborated by quantitative UHPLC-MS/MS analysis.
CONCLUSION
Dupilumab treatment tends to help shift the gut microbial dysbiosis in AD patients to a healthier state, along with improved intestinal tryptophan metabolism, suggesting the gut flora and its metabolites may mediate part of the synergistic therapeutic effects on the host.
Topics: Humans; Dermatitis, Atopic; Gastrointestinal Microbiome; Tryptophan; Dysbiosis; Tandem Mass Spectrometry; China; Antibodies, Monoclonal, Humanized
PubMed: 38493690
DOI: 10.1016/j.intimp.2024.111867 -
Nutrients Feb 2024Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with...
Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with multiple biological activities. This study aims to investigate the effects of C3G isolated from black rice on ALD and explore the potential mechanism. C57BL/6J mice (male) were fed with standard diet (CON) and Lieber-DeCarli liquid-fed (Eth) or supplemented with a 100 mg/kg/d C3G Diet (Eth-C3G), respectively. Our results showed that C3G could effectively ameliorate the pathological structure and liver function, and also inhibited the accumulation of liver lipids. C3G supplementation could partially alleviate the injury of intestinal barrier in the alcohol-induced mice. C3G supplementation could increase the abundance of , meanwhile, the abundances of , , , , , , , , , , , were decreased. Spearman's correlation analysis showed that 12 distinct genera were correlated with blood lipid levels. Non-targeted metabolic analyses of cecal contents showed that C3G supplementation could affect the composition of intestinal metabolites, particularly bile acids. In conclusion, C3G can attenuate alcohol-induced liver injury by modulating the gut microbiota and metabolites, suggesting its potential as a functional food ingredient against alcoholic liver disease.
Topics: Mice; Male; Animals; Anthocyanins; Gastrointestinal Microbiome; Mice, Inbred C57BL; Liver; Liver Diseases, Alcoholic; Glucosides
PubMed: 38474822
DOI: 10.3390/nu16050694 -
Neurobiology of Disease Apr 2024Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal...
Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal phase of AD. Free water (FW) imaging estimates the extracellular water content and has been used to study neuroinflammation across several neurological diseases including AD. Recently, the role of gut microbiota has been implicated in the pathogenesis of AD. The relationship between FW imaging and gut microbiota was examined in patients with AD and MCI. Fifty-six participants underwent neuropsychological assessments, FW imaging, and gut microbiota analysis targeting the bacterial 16S rRNA gene. They were categorized into the cognitively normal control (NC) (n = 19), MCI (n = 19), and AD (n = 18) groups according to the neuropsychological assessments. The correlations of FW values, neuropsychological assessment scores, and the relative abundance of gut microbiota were analyzed. FW was higher in several white matter tracts and in gray matter regions, predominantly the frontal, temporal, limbic and paralimbic regions in the AD/MCI group than in the NC group. In the AD/MCI group, higher FW values in the temporal (superior temporal and temporal pole), limbic and paralimbic (insula, hippocampus and amygdala) regions were the most associated with worse neuropsychological assessment scores. In the AD/MCI group, FW values in these regions were negatively correlated with the relative abundances of butyrate-producing genera Anaerostipes, Lachnospiraceae UCG-004, and [Ruminococcus] gnavus group, which showed a significant decreasing trend in the order of the NC, MCI, and AD groups. The present study showed that increased FW in the gray matter regions related to cognitive impairment was associated with low abundances of butyrate producers in the AD/MCI group. These findings suggest an association between neuroinflammation and decreased levels of the short-chain fatty acid butyrate that is one of the major gut microbial metabolites having a potentially beneficial role in brain homeostasis.
Topics: Humans; Gray Matter; Alzheimer Disease; Gastrointestinal Microbiome; Butyrates; Neuroinflammatory Diseases; RNA, Ribosomal, 16S; Cognitive Dysfunction; Magnetic Resonance Imaging
PubMed: 38452948
DOI: 10.1016/j.nbd.2024.106464 -
Frontiers in Microbiology 2023Contusion type of traumatic brain injury (TBI) is a major cause of locomotor disability and mortality worldwide. While post-TBI deleterious consequences are influenced...
INTRODUCTION
Contusion type of traumatic brain injury (TBI) is a major cause of locomotor disability and mortality worldwide. While post-TBI deleterious consequences are influenced by gender and gut dysbiosis, the sex-specific importance of commensal gut microbiota is underexplored after TBI. In this study, we investigated the impact of controlled cortical impact (CCI) injury on gut microbiota signature in a sex-specific manner in mice.
METHODS
We depleted the gut microflora of male and female C57BL/6 mice using antibiotic treatment. Thereafter, male mice were colonized by the gut microbiota of female mice and vice versa, employing the fecal microbiota transplantation (FMT) method. CCI surgery was executed using a stereotaxic impactor (Impact One™). For the 16S rRNA gene amplicon study, fecal boli of mice were collected at 3 days post-CCI (dpi).
RESULTS AND DISCUSSION
CCI-operated male and female mice exhibited a significant alteration in the genera of , , . At the species level, less abundance of and was observed in female mice, implicating the importance of sex-specific bacteriotherapy in CCI-induced neurological deficits. FMT from female donor mice to male mice displayed an increase in genera of , , and and species of and . Female FMT-recipient mice from male donors showed an upsurge in the genus and species of , , and . These results suggest that the post-CCI neurological complications may be influenced by the differential gut microbiota perturbation in male and female mice.
PubMed: 38410824
DOI: 10.3389/fmicb.2023.1336537 -
Journal of Microbiology and... Mar 2024In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact...
In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact of () on DN. Eight-week-old male KK-Ay mice were administered antibiotic cocktails for a duration of two weeks, followed by oral administration of for an additional eight weeks. Our study revealed significant changes in the gut microbiota during both the initiation and progression of DN. Specifically, we observed a notable increase in the abundance of Clostridia at the class level, higher levels of Lachnospirales and Oscillospirales at the order level, and a marked decrease in Clostridia_UCG-014 in DN group. Additionally, there was a significant increase in the abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Moreover, oral administration of effectively aggravated kidney pathology in DN mice, accompanied by elevated levels of urea nitrogen (UN), creatinine (Cr), and urine protein. Furthermore, administration resulted in down-regulation of tight junction proteins such as Claudin-1, Occludin, and ZO-1, as well as increased levels of uremic toxins in urine and serum samples. Additionally, our study demonstrated that orally administered up-regulated the expression of inflammatory factors, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) and Interleukin (IL)-6. These changes indicated the involvement of the gut-kidney axis in DN, and may worsen diabetic nephropathy by affecting uremic toxin levels and promoting inflammation in DN.
Topics: Mice; Male; Animals; Diabetic Nephropathies; Ruminococcus; Gastrointestinal Microbiome; Clostridiales; Diabetes Mellitus
PubMed: 38346799
DOI: 10.4014/jmb.2310.10028 -
Scientific Reports Feb 2024High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and...
High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and cardiovascular diseases. In contrast, exercise can positively influence gut microbial diversity and is linked to a decreased inflammatory state. To understand the gut microbial variations associated with exercise and high-fat diet over time, we conducted a longitudinal study to examine the effect of covariates on gut microbial diversity and composition. Young mice were divided into four groups: Chow-diet (CHD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise only (EXE) and underwent experimental intervention for 12 weeks. Fecal samples at week 0 and 12 were collected for DNA extraction, followed by 16S library preparation and sequencing. Data were analyzed using QIIME 2, R and MicrobiomeAnalyst. The Bacteroidetes-to-Firmicutes ratio decreased fivefold in the HFD and HFX groups compared to that in the CHD and EXE groups and increased in the EXE group over time. Alpha diversity was significantly increased in the EXE group longitudinally (p < 0.02), whereas diversity (Shannon, Faith's PD, and Fisher) and richness (ACE) was significantly reduced in the HFD (p < 0.005) and HFX (p < 0.03) groups over time. Beta diversity, based on the Jaccard, Bray-Curtis, and unweighted UniFrac distance metrics, was significant among the groups. Prevotella, Paraprevotella, Candidatus arthromitus, Lactobacillus salivarius, L. reuteri, Roseburia, Bacteroides uniformis, Sutterella, and Corynebacterium were differentially abundant in the chow-diet groups (CHD and EXE). Exercise significantly reduced the proportion of taxa characteristic of a high-fat diet, including Butyricimonas, Ruminococcus gnavus, and Mucispirillum schaedleri. Diet, age, and exercise significantly contributed to explaining the bacterial community structure and diversity in the gut microbiota. Modulating the gut microbiota and maintaining its stability can lead to targeted microbiome therapies to manage chronic and recurrent diseases and infections.
Topics: Mice; Animals; Diet, High-Fat; Gastrointestinal Microbiome; Longitudinal Studies; Obesity; Bacteroidetes; Mice, Inbred C57BL
PubMed: 38332014
DOI: 10.1038/s41598-024-52852-4 -
Gastroenterology Jun 2024Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut... (Review)
Review
Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut interaction, to seek medical attention. It represents a substantial burden to patients and is associated with anxiety, depression, reductions in quality of life, and impaired social functioning, as well as increased direct and indirect health care costs to society. Unfortunately, the diagnosis and treatment of chronic visceral pain is difficult, in part because our understanding of the underlying pathophysiologic basis is incomplete. In this review, we highlight recent advances in peripheral pain signaling and specific physiologic and pathophysiologic preclinical mechanisms that result in the sensitization of peripheral pain pathways. We focus on preclinical mechanisms that have been translated into treatment approaches and summarize the current evidence base for directing treatment toward these mechanisms of chronic visceral pain derived from clinical trials. The effective management of chronic visceral pain remains of critical importance for the quality of life of suffers. A deeper understanding of peripheral pain mechanisms is necessary and may provide the basis for novel therapeutic interventions.
Topics: Humans; Visceral Pain; Chronic Pain; Animals; Quality of Life; Signal Transduction
PubMed: 38325759
DOI: 10.1053/j.gastro.2024.01.045 -
BMC Psychiatry Jan 2024Major depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been...
BACKGROUND
Major depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been hypothesized to be involved in MDD through gut-brain axis signaling. Moreover, antidepressants display antibacterial properties in the gastrointestinal tract. The aim of this study was to compare the gut microbiota and systemic inflammatory profile of young patients with MDD before and after initiation of antidepressant treatment and/or psychotherapy in comparison with a non-depressed control group (nonMDD).
METHODS
Fecal and blood samples were collected at baseline and at follow-up after four and twelve weeks, respectively. Patients started treatment immediately after collection of the baseline samples. The gut microbiota was characterized by 16 S rRNA gene sequencing targeting the hypervariable V4 region. Plasma levels of 49 unique immune markers were assessed using Mesoscale.
RESULTS
In total, 27 MDD patients and 32 nonMDD controls were included in the study. The gut microbiota in the baseline samples of MDD versus nonMDD participants did not differ regarding α- or β-diversity. However, there was a higher relative abundance of the genera Ruminococcus gnavus group, and a lower relative abundance of the genera Desulfovibrio, Tyzzerella, Megamonas, Olsenella, Gordonibacter, Allisonella and Rothia in the MDD group compared to the nonMDD group. In the MDD group, there was an increase in the genera Rothia, Desulfovibrio, Gordinobacteer and Lactobacillus, while genera belonging to the Firmicutes phylum were found depleted at twelve weeks follow-up compared to baseline. In the MDD group, IL-7, IL-8 and IL-17b levels were elevated compared to the nonMDD group at baseline. Furthermore, MDI score in the MDD group was found to correlate with Bray-Curtis dissimilarity at baseline, and several inflammatory markers at both baseline and after initiation of antidepressant treatment.
CONCLUSION
Several bacterial taxa differed between the MDD group and the nonMDD group at baseline and changed in relative abundance during antidepressant treatment and/or psychotherapy. The MDD group was furthermore found to have a pro-inflammatory profile compared to the nonMDD group at baseline. Further studies are required to investigate the gut microbiota and pro-inflammatory profile of patients with MDD.
Topics: Humans; Depressive Disorder, Major; Gastrointestinal Microbiome; Antidepressive Agents; Cognition; Psychotherapy
PubMed: 38297265
DOI: 10.1186/s12888-024-05547-z