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Frontiers in Microbiology 2024Alcoholic liver disease (ALD) is exacerbated by disruptions in intestinal microecology and immune imbalances within the gut-liver axis. The present study assesses the...
BACKGROUND
Alcoholic liver disease (ALD) is exacerbated by disruptions in intestinal microecology and immune imbalances within the gut-liver axis. The present study assesses the therapeutic potential of combining () with inosine in alleviating alcohol-induced liver injury.
METHODS
Male C57BL/6 mice, subjected to a Lieber-DeCarli diet with 5% alcohol for 4 weeks, served as the alcoholic liver injury model. Various analyzes, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), ELISA, immunochemistry, 16S rRNA gene sequencing, and flow cytometry, were employed to evaluate liver injury parameters, intestinal barrier function, microbiota composition, and immune responses.
RESULTS
Compared to the model group, the and inosine groups exhibited significantly decreased alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide (LPS) levels, reduced hepatic fat deposition and neutrophil infiltration, alleviated oxidative stress and inflammation, and increased expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). These effects were further pronounced in the and inosine combination group compared to individual treatments. While alcohol feeding induced intestinal dysbiosis and gut barrier disruption, the combined treatment reduced the abundance of harmful bacteria () induced by alcohol consumption, promoting the growth of butyrate-producing bacteria (Akkermansia, Lactobacillus, and Clostridium IV). Flow cytometry revealed that alcohol consumption reduced T regulatory (Treg) populations while increasing those of T-helper (Th) 1 and Th17, which were restored by combined with inosine treatment. Moreover, and inosine combination increased the expression levels of intestinal CD39, CD73, and adenosine A2A receptor (A2AR) along with enhanced proportions of CD4CD39Treg and CD4CD73Treg cells in the liver and spleen. The A2AR antagonist KW6002, blocked the beneficial effects of the and inosine combination on liver injury in ALD mice.
CONCLUSION
This study reveals that the combination of and inosine holds promise for ameliorating ALD by enhancing the gut ecosystem, improving intestinal barrier function, upregulating A2AR, CD73, and CD39 expression, modulating Treg cells functionality, and regulating the imbalance of Treg/Th17/Th1 cells, and these beneficial effects are partly A2AR-dependent.
PubMed: 38572243
DOI: 10.3389/fmicb.2024.1355225 -
International Journal of Molecular... Feb 2024Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored...
Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.
Topics: Humans; Animals; Mice; Irritable Bowel Syndrome; Dermatitis, Atopic; Dysbiosis; Gastrointestinal Microbiome; Feces; Fecal Microbiota Transplantation; Inflammation
PubMed: 38473999
DOI: 10.3390/ijms25052753 -
Frontiers in Molecular Neuroscience 2024Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term...
INTRODUCTION
Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term dysbiosis of the gastrointestinal microbiome with significant alterations in composition and predicted functional consequences.
METHODS
Working with participants from past research, metagenomic stability of the TBI- associated fecal microbiome (FMB) was evaluated by custom qPCR array comparing a fecal sample from 2015 to one collected in 2020. Metatranscriptomics identified differently expressed bacterial genes and biochemical pathways in the TBI FMB. Microbiota that contributed the largest RNA amounts identified a set of core bacteria most responsible for functional consequences of the TBI FMB.
RESULTS
A remarkably stable FMB metagenome with significant similarity (two-tail Spearman nonparametric correlation < 0.001) was observed between 2015 and 2020 fecal samples from subjects with TBI. Comparing the 2020 TBI FMB metagenome to FMBs from healthy controls confirmed and extended the dysbiotic genera and species. Abundance differences between average TBI and healthy FMBs revealed . spp., spp., spp., and Ordoribacter spp. were significantly different. Functionally, the genus contributed the highest percentage of RNA sequences in control FMBs followed by the genus as the second highest contributor. In the TBI FMB, the genus contributed the most RNA followed by the genus. and were distinct in the top 10 contributing genera in the TBI FMB while and were unique to the top 10 in controls. Comparing RNA profiles, TBI samples had ∼1.5 fold more expressed genes with almost 700 differently expressed genes (DEGs) mapped to over 100 bacterial species. Bioinformatic analysis associated DEGs with pathways led identifying 311 functions in the average TBI FMB profile and 264 in the controls. By average profile comparison, 30 pathways had significantly different abundance ( < 0.05, -test) or were detected in >80% of the samples in only one of the cohorts (binary distinction).
DISCUSSION
Functional differences between TBI and healthy control FMBs included amino acid metabolism, energy and carbon source usage, fatty acid metabolism, bacterial cell wall component production and nucleic acid synthesis and processing pathways. Together these data shed light on the functional consequences of the dysbiotic TBI FMB decades after injury.
PubMed: 38544523
DOI: 10.3389/fnmol.2024.1341808 -
European Journal of Medical Research Nov 2023Irritable bowel syndrome (IBS) is a prevalent gastrointestinal (GI) tract disorder. Although the main reason for IBS is not clear, the interaction between intestinal...
Irritable bowel syndrome (IBS) is a prevalent gastrointestinal (GI) tract disorder. Although the main reason for IBS is not clear, the interaction between intestinal microorganisms and the gut barrier seems to play an important role in pathogenesis of IBS. The current study aimed to investigate the effect of Blastocystis on the gut microbiota profile and the circulation levels of microRNA (mir)-16 of IBS patients compared to healthy subjects. Stool and blood samples were collected from 80 participants including 40 samples from each IBS and healthy group. Upon DNA extraction from stool samples, barcoding region and quantitative real-time PCR were analyzed to investigate Blastocystis and the microbiota profile, respectively. RNA was extracted from serum samples of included subjects and the expression of mir-16 was evaluated using stem-loop protocol and qreal-time PCR. Significant changes between IBS patients and healthy controls was observed in Firmicutes, Actinobacteria, Faecalibacterium, and Alistipes. In IBS patients, the relative abundance of Bifidobacteria was directly correlated with the presence of Blastocystis, while Alistipes was decreased with Blastocystis. Lactobacillus was significantly increased in Blastocystis carriers. In healthy subjects, the relative abundance of Bifidobacteria was decreased, but Alistipes was increased in Blastocystis carriers. The changes in the Firmicutes/Bacteroidetes ratio was not significant in different groups. The relative expression of mir-16 in Blastocystis-negative IBS patients and healthy carriers was significantly overexpressed compared to control group. The presence of Blastocystis, decreased the relative expression of mir-16 in IBS patients compared to Blastocystis-negative IBS patients. The present study revealed that Blastocystis has the ability to change the abundance of some phyla/genera of bacteria in IBS and healthy subjects. Moreover, Blastocystis seems to modulate the relative expression of microRNAs to control the gut atmosphere, apply its pathogenicity, and provide a favor niche for its colonization.
Topics: Humans; Irritable Bowel Syndrome; Blastocystis Infections; Circulating MicroRNA; Case-Control Studies; Blastocystis; Microbiota; MicroRNAs
PubMed: 37932792
DOI: 10.1186/s40001-023-01441-8 -
Applied Microbiology and Biotechnology Jun 2024The gastrointestinal tract (GIT) is stationed by a dynamic and complex microbial community with functions in digestion, metabolism, immunomodulation, and reproduction....
The gastrointestinal tract (GIT) is stationed by a dynamic and complex microbial community with functions in digestion, metabolism, immunomodulation, and reproduction. However, there is relatively little research on the composition and function of microorganisms in different GIT segments in dairy goats. Herein, 80 chyme samples were taken from ten GIT sites of eight Xinong Saanen dairy goats and then analyzed and identified the microbial composition via 16S rRNA V1-V9 amplicon sequencing. A total of 6669 different operational taxonomic units (OTUs) were clustered, and 187 OTUs were shared by ten GIT segments. We observed 264 species belonging to 23 different phyla scattered across ten GITs, with Firmicutes (52.42%) and Bacteroidetes (22.88%) predominating. The results revealed obvious location differences in the composition, diversity, and function of the GIT microbiota. In LEfSe analysis, unidentified_Lachnospiraceae and unidentified_Succinniclassicum were significantly enriched in the four chambers of stomach, with functions in carbohydrate fermentation to compose short-chain fatty acids. Aeriscardovia, Candidatus_Saccharimonas, and Romboutsia were significantly higher in the foregut, playing an important role in synthesizing enzymes, amino acids, and vitamins and immunomodulation. Akkermansia, Bacteroides, and Alistipes were significantly abundant in the hindgut to degrade polysaccharides and oligosaccharides, etc. From rumen to rectum, α-diversity decreased first and then increased, while β-diversity showed the opposite trend. Metabolism was the major function of the GIT microbiome predicted by PICRUSt2, but with variation in target substrates along the regions. In summary, GIT segments play a decisive role in the composition and functions of microorganisms. KEY POINTS: • The jejunum and ileum were harsh for microorganisms to colonize due to the presence of bile acids, enzymes, faster chyme circulation, etc., exhibiting the lowest α-diversity and the highest β-diversity. • Variability in microbial profiles between the three foregut segments was greater than four chambers of stomach and hindgut, with a higher abundance of Firmicutes dominating than others. • Dairy goats dominated a higher abundance of Kiritimatiellaeota than cows, which was reported to be associated with fatty acid synthesis.
Topics: Animals; Goats; Gastrointestinal Microbiome; Gastrointestinal Tract; RNA, Ribosomal, 16S; Bacteria; Phylogeny; DNA, Bacterial; Biodiversity; Female
PubMed: 38822843
DOI: 10.1007/s00253-024-13200-8 -
Frontiers in Microbiology 2023Heat stress can affect the production of poultry through complex interactions between genes, metabolites and microorganisms. At present, it is unclear how heat stress...
INTRODUCTION
Heat stress can affect the production of poultry through complex interactions between genes, metabolites and microorganisms. At present, it is unclear how heat stress affects genetic, metabolic and microbial changes in poultry, as well as the complex interactions between them.
METHODS
Thus, at 28 days of age a total of 200 Arbor Acres broilers with similar body weights were randomly divided into the control (CON) and heat stress treatment (HS). There were 5 replicates in CON and HS, respectively, 20 per replication. From the 28-42 days, the HS was kept at 31 ± 1°C (9:00-17:00, 8 h) and other time was maintained at 21 ± 1°C as in the CON. At the 42nd day experiment, we calculated the growth performance ( = 8) of broilers and collected 3 and 6 cecal tissues for transcriptomic and metabolomic investigation and 4 cecal contents for metagenomic investigation of each treatment.
RESULTS AND DISCUSSION
The results indicate that heat stress significantly reduced the average daily gain and body weight of broilers (value of < 0.05). Transcriptome KEGG enrichment showed that the differential genes were mainly enriched in the NF-kB signaling pathway. Metabolomics results showed that KEGG enrichment showed that the differential metabolites were mainly enriched in the mTOR signaling pathway. 16S rDNA amplicon sequencing results indicated that heat stress increased the relative abundance of decreased the relative abundance of . Multi-omics analysis showed that the co-participating pathway of differential genes, metabolites and microorganisms KEGG enrichment was purine metabolism. Pearson correlation analysis found that ornithine was positively correlated with , and , and negatively correlated with . PE was negatively correlated with and , and positively with . In conclusion, heat stress can generate large amounts of reactive oxygen and increase the types of harmful bacteria, reduce intestinal nutrient absorption and antioxidant capacity, and thereby damage intestinal health and immune function, and reduce growth performance indicators. This biological process is manifested in the complex regulation, providing a foundational theoretical basis for solving the problem of heat stress.
PubMed: 37795292
DOI: 10.3389/fmicb.2023.1244004 -
Microbiology Spectrum Apr 2024Altered gut microbiota and metabolites are important for non-alcoholic fatty liver disease (NAFLD) in children. We aimed to comprehensively examine the effects of gut...
UNLABELLED
Altered gut microbiota and metabolites are important for non-alcoholic fatty liver disease (NAFLD) in children. We aimed to comprehensively examine the effects of gut metabolites on NAFLD progression. We performed integrative metabolomics (untargeted discovery and targeted validation) analysis of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and obesity in children. Fecal samples were collected from 75 subjects in the discovery cohort (25 NAFL, 25 NASH, and 25 obese control children) and 145 subjects in an independent validation cohort (53 NAFL, 39 NASH, and 53 obese control children). Among 2,491 metabolites, untargeted metabolomics revealed a complete NAFLD metabolic map containing 318 increased and 123 decreased metabolites. Then, machine learning selected 65 important metabolites that can distinguish the severity of the NAFLD. Furthermore, precision-targeted metabolomics selected 5 novel gut metabolites from 20 typical metabolites. The functionality of candidate metabolites was validated in hepatocyte cell lines. In the end, this study annotated two novel elevated pathogenic metabolites (dodecanoic acid and creatinine) and a relationship between depleted protective gut microbiota ( and ), increased inflammation (IL-1β), lipid metabolism (TG), and liver function (ALT and AST). This study demonstrates the role of novel gut metabolites (dodecanoic acid and creatinine), as the fatty acid metabolism regulator contributing to NAFLD development through its influence on inflammation and liver function.
IMPORTANCE
Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota ( and ) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.
Topics: Child; Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Creatinine; Pediatric Obesity; Biomarkers; Inflammation; Metabolomics; Liver
PubMed: 38445874
DOI: 10.1128/spectrum.05230-22 -
Poultry Science Dec 2023Litters, the composition of sand and peat rich in microbiota, are essential to trigger the dustbathing behavior of chickens. To investigate the effects of a dustbathing...
Effects of dustbathing environment on gut microbiota and expression of intestinal barrier and immune-related genes of adult laying hens housed individually in modified traditional cage.
Litters, the composition of sand and peat rich in microbiota, are essential to trigger the dustbathing behavior of chickens. To investigate the effects of a dustbathing environment (DE) on the intestinal health, gut microbiota, and immune responses of laying hens, a total of 72 healthy Hy-Line Brown laying hens at 69 wk of age (WOA) were housed individually in modified traditional cages and randomly divided into 2 groups: one group had free access to litters (CT), while the other one was restricted from litters (CC). The experiment lasted for 42 d. At the end of the experiment, the intestinal histomorphology and immune status of laying hens were determined, and the 16S rRNA sequencing method was used to assess the composition of the intestinal microbial community of birds. Intestinal histomorphology changed, including villus height and villus-to-crypt ratio significantly increased in the CT group (P < 0.01). DE reshaped the microbial community and increased the microbial richness with the higher indicators of Chao1 and observed species and the comparatively abundant beta diversity (P < 0.05). Ten genera, including Faecalibacterium and Coprococcus, declined in laying hens from the CT group (P < 0.05), while Alistipes increased in CT hens (P < 0.05) compared to those hens from the CC group. The expression levels of intestinal barrier-related genes of claudin-1, claudin-4, occludin, ZO-1, and ZO-2 and immune-related genes of IL-4, IL-6, IL-8, IFN-γ, IgA, TLR-2, and TLR-4 were significantly upregulated in the intestine of laying hens in CT group (P < 0.05). DE also increased the serum levels of IL-4, IL-6, IL-8, IFN-γ, and IgA (P < 0.01). The alteration of the gut microbiota by DE is closely related to host immune responses, including Lactobacillus positively correlated with IL-4 and IgA. Thus, a dustbathing environment can improve the welfare of laying hens by changing the intestinal histomorphology, immune response, and the gut microbial community.
Topics: Animals; Female; Gastrointestinal Microbiome; Chickens; Interleukin-6; RNA, Ribosomal, 16S; Interleukin-4; Interleukin-8; Immunoglobulin A; Animal Feed
PubMed: 37769487
DOI: 10.1016/j.psj.2023.103097 -
Gut Microbes 2024The gut microbiota plays a pivotal role in metabolic disorders, notably type 2 diabetes mellitus (T2DM). In this study, we investigated the synergistic potential of...
The gut microbiota plays a pivotal role in metabolic disorders, notably type 2 diabetes mellitus (T2DM). In this study, we investigated the synergistic potential of combining the effects of NBM7-1 (CKD1) with anti-diabetic medicines, Lobeglitazone (LO), Sitagliptin (SI), and Metformin (Met), to alleviate hyperglycemia in a diabetic mouse model. CKD1 effectively mitigated insulin resistance, hepatic steatosis, and enhanced pancreatic β-cell function, as well as fortifying gut-tight junction integrity. In the same way, SI-CKD1 and Met- CKD1 synergistically improved insulin sensitivity and prevented hepatic steatosis, as evidenced by the modulation of key genes associated with insulin signaling, β-oxidation, gluconeogenesis, adipogenesis, and inflammation by qRT-PCR. The comprehensive impact on modulating gut microbiota composition was observed, particularly when combined with Metformin. This combination induced an increase in the abundance of and related negatively to the T2DM incidence while reducing the causative species of , and . These alterations intervene in gut microbiota metabolites to modulate the level of butyrate, indole-3-acetic acid, propionate, and inflammatory cytokines and to activate the IL-22 pathway. However, it is meaningful that the combination of NBM7-1(CKD1) reduced the medicines' dose to the level of the maximal inhibitory concentrations (IC50). This study advances our understanding of the intricate relationship between gut microbiota and metabolic disorders. We expect this study to contribute to developing a prospective therapeutic strategy modulating the gut microbiota.
Topics: Mice; Animals; Diabetes Mellitus, Type 2; Up-Regulation; Diabetes Mellitus, Experimental; Gastrointestinal Microbiome; Metformin; Insulin Resistance
PubMed: 38391178
DOI: 10.1080/19490976.2024.2319889 -
Frontiers in Immunology 2024Previous studies have indicated a potential link between the gut microbiota and lymphoma. However, the exact causal interplay between the two remains an area of...
BACKGROUND
Previous studies have indicated a potential link between the gut microbiota and lymphoma. However, the exact causal interplay between the two remains an area of ambiguity.
METHODS
We performed a two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between gut microbiota and five types of lymphoma. The research drew upon microbiome data from a research project of 14,306 participants and lymphoma data encompassing 324,650 cases. Single-nucleotide polymorphisms were meticulously chosen as instrumental variables according to multiple stringent criteria. Five MR methodologies, including the inverse variance weighted approach, were utilized to assess the direct causal impact between the microbial exposures and lymphoma outcomes. Moreover, sensitivity analyses were carried out to robustly scrutinize and validate the potential presence of heterogeneity and pleiotropy, thereby ensuring the reliability and accuracy.
RESULTS
We discerned 38 potential causal associations linking genetic predispositions within the gut microbiome to the development of lymphoma. A few of the more significant results are as follows: Genus (OR = 0.619, 95% CI 0.438-0.873, = 0.006) demonstrated a potentially protective effect against Hodgkin's lymphoma (HL). Genus (OR = 0.473, 95% CI 0.278-0.807, = 0.006) was a protective factor for diffuse large B-cell lymphoma. Genus (OR = 0.541, 95% CI 0.341-0.857, = 0.009) exhibited suggestive protective effects against follicular lymphoma. Genus (OR = 0.354, 95% CI 0.198-0.631, = 0.0004) showed protective properties against T/NK cell lymphoma. The test indicated an absence of heterogeneity, and the MR-Egger test did not show significant horizontal polytropy. Furthermore, the leave-one-out analysis failed to identify any SNP that exerted a substantial influence on the overall results.
CONCLUSION
Our study elucidates a definitive causal link between gut microbiota and lymphoma development, pinpointing specific microbial taxa with potential causative roles in lymphomagenesis, as well as identifying probiotic candidates that may impact disease progression, which provide new ideas for possible therapeutic approaches to lymphoma and clues to the pathogenesis of lymphoma.
Topics: Mendelian Randomization Analysis; Humans; Gastrointestinal Microbiome; Polymorphism, Single Nucleotide; Lymphoma; Genetic Predisposition to Disease
PubMed: 38774867
DOI: 10.3389/fimmu.2024.1397485