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Nutrients Jun 2022The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but... (Review)
Review
The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but comparative literature is scarce. To fill this gap, we explored the contribution of the microbiota-gut-brain axis to the pathophysiology of seven brain-related diseases (attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, major depressive disorder, and bipolar disorder). In this article, we discussed changes in bacterial abundance and the metabolic implications of these changes on disease development and progression. Our central findings indicate that, mechanistically, all seven diseases are associated with a leaky gut, neuroinflammation, and over-activated microglial cells, to which gut-residing bacteria and their metabolites are important contributors. Patients show a pro-inflammatory shift in their colon microbiota, harbouring more Gram-negative bacteria containing immune-triggering lipopolysaccharides (LPS) in their cell walls. In addition, bacteria with pro-inflammatory properties (, , ) are found in higher abundances, whereas lower abundances of anti-inflammatory bacteria (, , , , , , , , ) are reported, when compared to healthy controls. On the metabolite level, aberrant levels of short-chain fatty acids (SCFAs) are involved in disease pathogenesis and are mostly found in lower quantities. Moreover, bacterial metabolites such as neurotransmitters (acetylcholine, dopamine, noradrenaline, GABA, glutamate, serotonin) or amino acids (phenylalanine, tryptophan) also play an important role. In the future, defined aberrations in the abundance of bacteria strains and altered bacterial metabolite levels could likely be possible markers for disease diagnostics and follow-ups. Moreover, they could help to identify novel treatment options, underlining the necessity for a deeper understanding of the microbiota-gut-brain axis.
Topics: Alzheimer Disease; Autism Spectrum Disorder; Bacteria; Brain; Depressive Disorder, Major; Dysbiosis; Humans
PubMed: 35807841
DOI: 10.3390/nu14132661 -
Cell Host & Microbe Feb 2023Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances,...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, and orthostatic intolerance. Here, we report a multi-omic analysis of a geographically diverse cohort of 106 cases and 91 healthy controls that revealed differences in gut microbiome diversity, abundances, functional pathways, and interactions. Faecalibacterium prausnitzii and Eubacterium rectale, which are both recognized as abundant, health-promoting butyrate producers in the human gut, were reduced in ME/CFS. Functional metagenomics, qPCR, and metabolomics of fecal short-chain fatty acids confirmed a deficient microbial capacity for butyrate synthesis. Microbiome-based machine learning classifier models were robust to geographic variation and generalizable in a validation cohort. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity. These findings demonstrate the functional nature of gut dysbiosis and the underlying microbial network disturbance in ME/CFS, providing possible targets for disease classification and therapeutic trials.
Topics: Humans; Fatigue Syndrome, Chronic; Gastrointestinal Microbiome; Butyrates; Bacteria; Metabolomics
PubMed: 36758522
DOI: 10.1016/j.chom.2023.01.004 -
Bio-protocol Apr 2020and species of the human gut microbiota play an important role in the maintaince of human health, partly by producing butyrate, the main energy source of our colonic...
and species of the human gut microbiota play an important role in the maintaince of human health, partly by producing butyrate, the main energy source of our colonic epithelial cells. However, our knowledge of the biochemistry and physiology of these bacteria has been limited by a lack of genetic manipulation techniques. Conjugative transposons previously introduced into species could not be easily modified, greatly limiting their applicability as genetic modification platforms. Modular plasmid shuttle vectors have previously been developed for species, which share a taxonomic order with and , raising the possibility that these vectors could be used in these organisms. Here, we describe an optimized conjugation protocol enabling the transfer of autonomously replicating plasmids from an donor strain into and . The modular nature of the plasmids and their ability to be maintained in the recipient bacterium by autonomous replication makes them ideal for investigating heterologous gene expression, and as a platform for other genetic tools including antisense RNA silencing or mobile group II interon gene disruption strategies.
PubMed: 33659545
DOI: 10.21769/BioProtoc.3575 -
Genome Biology Jun 2020Eubacterium rectale is one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome...
BACKGROUND
Eubacterium rectale is one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome investigations of this microbe have not been carried out.
RESULTS
Here, we leverage metagenomic assembly followed by a reference-based binning strategy to screen over 6500 gut metagenomes spanning geography and lifestyle and reconstruct over 1300 E. rectale high-quality genomes from metagenomes. We extend previous results of biogeographic stratification, identifying a new subspecies predominantly found in African individuals and showing that closely related non-human primates do not harbor E. rectale. Comparison of pairwise genetic and geographic distances between subspecies suggests that isolation by distance and co-dispersal with human populations might have contributed to shaping the contemporary population structure of E. rectale. We confirm that a relatively recently diverged E. rectale subspecies specific to Europe consistently lacks motility operons and that it is immotile in vitro, probably due to ancestral genetic loss. The same subspecies exhibits expansion of its carbohydrate metabolism gene repertoire including the acquisition of a genomic island strongly enriched in glycosyltransferase genes involved in exopolysaccharide synthesis.
CONCLUSIONS
Our study provides new insights into the population structure and ecology of E. rectale and shows that shotgun metagenomes can enable population genomics studies of microbiota members at a resolution and scale previously attainable only by extensive isolate sequencing.
Topics: Adolescent; Adult; Aged; Carbohydrate Metabolism; Child; Child, Preschool; Eubacterium; Gastrointestinal Microbiome; Genome, Bacterial; Glycosyltransferases; Humans; Infant; Metagenome; Middle Aged; Phylogeography; Young Adult
PubMed: 32513234
DOI: 10.1186/s13059-020-02042-y -
Frontiers in Immunology 2021The purpose of this study was to determine whether administration of the microorganism () could regulate dendritic cell (DC) activation and systemic inflammation in...
The purpose of this study was to determine whether administration of the microorganism () could regulate dendritic cell (DC) activation and systemic inflammation in herpes simplex virus type 1-induced Behçet's disease (BD). , butyrate-producing bacteria, was administered to BD mice. Peripheral blood leukocytes (PBL) and lymph node cells were isolated and analyzed by flow cytometry. 16S rRNA metagenomic analysis was performed in the feces of mice to determine the differences in the composition of the microbial population between normal and BD mice. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of DC activation marker CD83 positive cells was significantly increased in PBL of BD mice. Frequencies of CD83+ cells were also significantly increased in patients with active BD. 16S rRNA metagenomic analysis revealed different gut microbiota composition between normal and BD mice. The administration of to BD mice reduced the frequency of CD83+ cells and significantly increased the frequency of NK1.1+ cells with the improvement of symptoms. The co-administration of colchicine and also significantly reduced the frequency of CD83+ cells. Differences in gut microbiota were observed between normal mice and BD mice, and the administration of downregulated the frequency of CD83, which was associated with BD deterioration. These data indicate that could be a new therapeutic adjuvant for BD management.
Topics: Administration, Oral; Adult; Animals; Antigens, CD; Bacteria; Behcet Syndrome; Butyrates; Colchicine; Combined Modality Therapy; Dendritic Cells; Disease Models, Animal; Down-Regulation; Eubacterium; Fecal Microbiota Transplantation; Female; Gastrointestinal Microbiome; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulins; Inflammation; Interleukin-17; Killer Cells, Natural; Male; Membrane Glycoproteins; Metagenome; Mice; Middle Aged; RNA, Ribosomal, 16S; Random Allocation; Ribotyping; Severity of Illness Index; CD83 Antigen
PubMed: 34531862
DOI: 10.3389/fimmu.2021.712312 -
Research (Washington, D.C.) 2023Natural killer (NK) cells, as key immune cells, play essential roles in tumor cell immune escape and immunotherapy. Accumulating evidence has demonstrated that the gut...
Natural killer (NK) cells, as key immune cells, play essential roles in tumor cell immune escape and immunotherapy. Accumulating evidence has demonstrated that the gut microbiota community affects the efficacy of anti-PD1 immunotherapy and that remodeling the gut microbiota is a promising strategy to enhance anti-PD1 immunotherapy responsiveness in advanced melanoma patients; however, the details of the mechanism remain elusive. In this study, we found that was significantly enriched in melanoma patients who responded to anti-PD1 immunotherapy and that a high abundance was related to longer survival in melanoma patients. Furthermore, administration of remarkably improved the efficacy of anti-PD1 therapy and increased the overall survival of tumor-bearing mice; moreover, application of led to a significant accumulation of NK cells in the tumor microenvironment. Interestingly, conditioned medium isolated from an culture system dramatically enhanced NK cell function. Gas chromatography-mass spectrometry/ultrahigh performance liquid chromatography-tandem mass spectrometry-based metabolomic analysis showed that l-serine production was significantly decreased in the group; moreover, administration of an l-serine synthesis inhibitor dramatically increased NK cell activation, which enhanced anti-PD1 immunotherapy effects. Mechanistically, supplementation with l-serine or application of an l-serine synthesis inhibitor affected NK cell activation through Fos/Fosl. In summary, our findings reveal the role of bacteria-modulated serine metabolic signaling in NK cell activation and provide a novel therapeutic strategy to improve the efficacy of anti-PD1 immunotherapy in melanoma.
PubMed: 37223471
DOI: 10.34133/research.0127 -
Microbiology Spectrum Apr 2024Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the... (Observational Study)
Observational Study
UNLABELLED
Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of in both PsO and PsA patients, with PsA patients exhibiting even lower levels of than PsO patients. Additionally, two species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients.
IMPORTANCE
In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of and related functional genes among psoriatic patients, including those with psoriatic arthritis. may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.
Topics: Humans; Arthritis, Psoriatic; Eubacterium; Gastrointestinal Microbiome; Psoriasis; Feces
PubMed: 38441468
DOI: 10.1128/spectrum.01154-23 -
Chonnam Medical Journal Sep 2022Coronavirus disease 2019 (COVID-19) is an infectious disease with a wide range of respiratory and extrapulmonary symptoms, as well as gastrointestinal symptoms. Despite... (Review)
Review
Coronavirus disease 2019 (COVID-19) is an infectious disease with a wide range of respiratory and extrapulmonary symptoms, as well as gastrointestinal symptoms. Despite recent research linking gut microbiota to infectious diseases like influenza, minimal information is known about the gut microbiota's function in COVID-19 pathogenesis. Studies suggest that dysbiosis of the gut microbiota and gut barrier dysfunction may play a role in COVID-19 pathogenesis by disrupting host immune homeostasis. Regardless of whether patients had taken medication or disease severity, the gut microbiota composition was significantly altered in COVID-19 patients compared to non-COVID-19 individuals. Several gut commensals with recognized immunomodulatory potential, such as , , and bifidobacteria, were underrepresented in patients and remained low in samples taken several weeks after disease resolution. Furthermore, even with disease resolution, dysbiosis in the gut microbiota may contribute to chronic symptoms, underscoring the need to learn more about how gut microbes play a role in inflammation and COVID-19.
PubMed: 36245770
DOI: 10.4068/cmj.2022.58.3.96 -
Gut Pathogens Jan 2021Inflammatory bowel disease caused by microbial dysbiosis is an important factor contributing to colorectal cancer (CRC) initiation. The 'driver-passenger' model in human...
BACKGROUND
Inflammatory bowel disease caused by microbial dysbiosis is an important factor contributing to colorectal cancer (CRC) initiation. The 'driver-passenger' model in human gut microbial dysbiosis suggests that 'driver' bacteria may colonize with low relative abundance on tumor site but persistently induce chronic change in normal intestinal epithelium and initiate CRC. They are gradually replaced by 'passenger' bacteria later on, due to their low adaptability to the on-tumor site niche.
RESULTS
To reveal site-specific bacterial taxon markers in CRC patients, we analyzed the gut mucosal microbiome of 75 paired samples of on-tumor and tumor-adjacent sites, 75 off-tumor sites, and 26 healthy controls. Linear discriminant analysis of relative abundance profiles revealed unique bacterial taxon distribution correlated with specific tumor sites, with Eubacterium having the distribution characteristic of potential driver bacteria. We further show that Eubacterium rectale endotoxin activates the transcription factor NF-κΒ, which regulates multiple aspects of innate and adaptive immune responses in normal colon epithelial cells. Unlike the 'passenger' bacterium Fusobacterium nucleatum, E. rectale promotes dextran sodium sulfate-induced colitis in Balb/c mice.
CONCLUSIONS
Our findings reveal that E. rectale functions as a 'driver' bacterium and contributes to cancer initiation via promoting inflammation.
PubMed: 33436075
DOI: 10.1186/s13099-020-00396-z -
Genes Oct 2020Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to...
Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to identify the nutrient utilization- and short-chain fatty acid (SCFA) production potential of gut microbes in infants during the first year of life. Stool samples were obtained from mothers at 18 weeks of pregnancy and from infants at birth (first stool) at 3, 6, and 12-months of age from the general population-based PreventADALL cohort. We identified the taxonomic and SCFA composition in 100 mother-child pairs. The SCFA production and substrate utilization potential of gut microbes were observed by multiomics (shotgun sequencing and proteomics) on six infants. We found a four-fold increase in relative butyrate levels from 6 to 12 months of infant age. The increase was correlated to and its bacterial network, and relative abundance, while low butyrate at 12 months was correlated to and its associated network of bacteria. Both and expressed enzymes needed for butyrate production and enzymes related to dietary fiber degradation, while expressed mucus-, fucose, and human milk oligosaccharides (HMO)-related degradation enzymes. Therefore, we believe that the presence of its network, and are key bacteria in the transition from an infant- to an adult-like gut microbiota with respect to butyrate production. Our results indicate that the transition from an infant- to an adult-like gut microbiota with respect to butyrate producing bacteria, occurs between 6 and 12 months of infant age. The bacteria associated with the increased butyrate ratio/levels were and , which potentially utilize a variety of dietary fibers based on the glycoside hydrolases (GHs) expressed. with a negative association to butyrate potentially utilizes mucin, fucose, and HMO components. This knowledge could have future importance in understanding how microbial metabolites can impact infant health and development.
Topics: Butyrates; Clostridiales; Coenzyme A-Transferases; Eubacterium; Fatty Acids, Volatile; Gastrointestinal Microbiome; Humans; Infant
PubMed: 33105702
DOI: 10.3390/genes11111245