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Journal of Neuroinflammation May 2024The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion,...
BACKGROUND
The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls.
METHODS
The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied.
RESULTS
Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IV biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test).
CONCLUSION
In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.
Topics: Humans; HLA-B27 Antigen; Female; Male; Gastrointestinal Microbiome; Middle Aged; Uveitis, Anterior; Adult; Case-Control Studies; Aged
PubMed: 38715051
DOI: 10.1186/s12974-024-03109-4 -
BMC Microbiology Apr 2024Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases....
BACKGROUND
Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis.
RESULTS
A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium.
CONCLUSION
Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.
Topics: Humans; Stomach Neoplasms; Male; Female; Middle Aged; Gastritis; Feces; Metagenome; Bacteria; Aged; Gastrointestinal Microbiome; Adult
PubMed: 38658841
DOI: 10.1186/s12866-024-03219-2 -
Food Science & Nutrition Apr 2024Overweight and obesity are closely linked to gut dysbiosis/dysmetabolism and disrupted De-Ritis ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT)...
Overweight and obesity are closely linked to gut dysbiosis/dysmetabolism and disrupted De-Ritis ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio], which may contribute to chronic noncommunicable diseases onset. Concurrently, extensive research explores nutraceuticals, and health-enhancing supplements, for disease prevention or treatment. Thus, sedentary overweight volunteers were double-blind randomized into two groups: Novel Nutraceutical_(S) (without silymarin) and Novel Nutraceutical (with silymarin). Experimental formulations were orally administered twice daily over 180 consecutive days. We evaluated fecal gut microbiota, based on partial 16S rRNA sequences, biochemistry and endocrine markers, steatosis biomarker (AST/ALT ratio), and anthropometric parameters. Post-supplementation, only the Novel Nutraceutical group reduced (Firmicutes), Firmicutes/Bacteroidetes ratio (F/B ratio), and De-Ritis ratio, while elevating and (Bacteroidetes) in Brazilian sedentary overweight volunteers after 180 days. In summary, the results presented here allow us to suggest the gut microbiota as the action mechanism of the Novel Nutraceutical promoting metabolic hepatic recovery in obesity/overweight non-drug interventions.
PubMed: 38628220
DOI: 10.1002/fsn3.3927 -
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 -
MSystems Apr 2024The gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein...
The gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein diets are used for specific populations or indications, mainly weight loss. In this study, we investigated the effect of protein supplementation on , a Gram-negative gut symbiont. The supplementation with whey proteins led to a significant increase in growth rate, final biomass, and short-chain fatty acids production. A comprehensive genomic analysis revealed that possesses a set of 156 proteases with putative intracellular and extracellular localization and allowed to identify amino acid transporters and metabolic pathways. We developed a fully curated genome-scale metabolic model of that incorporated its proteolytic activity and simulated its growth and production of fermentation-related metabolites in response to the different growth media. We validated the model by comparing the predicted phenotype to experimental data. The model accurately predicted 's growth and metabolite production ( = 0.92 for the training set and = 0.89 for the validation set). We found that accounting for both ATP consumption related to proteolysis, and whey protein accessibility is necessary for accurate predictions of metabolites production. These results provide insights into 's adaptation to a high-protein diet and its ability to utilize proteins as a source of nutrition. The proposed model provides a useful tool for understanding the feeding mechanism of in the gut microbiome.IMPORTANCEMicrobial proteolysis is understudied despite the availability of dietary proteins for the gut microbiota. Here, the proteolytic potential of the gut symbiont was analyzed for the first time using pan-genomics. This sketches a well-equipped bacteria for protein breakdown, capable of producing 156 different proteases with a broad spectrum of cleavage targets. This functional potential was confirmed by the enhancement of growth and metabolic activities at high protein levels. Proteolysis was included in a metabolic model which was fitted with the experiments and validated on external data. This model pinpoints the links between protein availability and short-chain fatty acids production, and the importance for to gain access to glutamate and asparagine to promote growth. This integrated approach can be generalized to other symbionts and upscaled to complex microbiota to get insights into the ecological impact of proteins on the gut microbiota.
Topics: Humans; Proteolysis; Bacteria; Fatty Acids, Volatile; Peptide Hydrolases; Bacteroides
PubMed: 38517169
DOI: 10.1128/msystems.00153-24 -
Scientific Reports Feb 2024Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota...
Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota production of short-chain fatty acids (SCFAs) has been implicated in type 2 diabetes mellitus (T2DM) disease progression. Most microbiome studies focus on ethnic majorities. This study aims to understand how the microbiome differs between an ethnic majority (the Dutch) and minority (the South-Asian Surinamese (SAS)) group with a lower and higher prevalence of T2DM, respectively. Microbiome data from the Healthy Life in an Urban Setting (HELIUS) cohort were used. Two age- and gender-matched groups were compared: the Dutch (n = 41) and SAS (n = 43). Microbial community compositions were generated via DADA2. Metrics of microbial diversity and similarity between groups were computed. Biomarker analyses were performed to determine discriminating taxa. Bacterial co-occurrence networks were constructed to examine ecological patterns. A tight microbiota cluster was observed in the Dutch women, which overlapped with some of the SAS microbiota. The Dutch gut contained a more interconnected microbial ecology, whereas the SAS network was dispersed, i.e., contained fewer inter-taxonomic correlational relationships. Bacteroides caccae, Butyricicoccus, Alistipes putredinis, Coprococcus comes, Odoribacter splanchnicus, and Lachnospira were enriched in the Dutch gut. Haemophilus, Bifidobacterium, and Anaerostipes hadrus discriminated the SAS gut. All but Lachnospira and certain strains of Haemophilus are known to produce SCFAs. The Dutch gut microbiome was distinguished from the SAS by diverse, differentially abundant SCFA-producing taxa with significant cooperation. The dynamic ecology observed in the Dutch was not detected in the SAS. Among several potential gut microbial biomarkers, Haemophilus parainfluenzae likely best characterizes the ethnic minority group, which is more predisposed to T2DM. The higher prevalence of T2DM in the SAS may be associated with the gut dysbiosis observed.
Topics: Humans; Female; Ethnicity; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Adenosine Deaminase; Minority Groups; Intercellular Signaling Peptides and Proteins; Fatty Acids, Volatile
PubMed: 38403716
DOI: 10.1038/s41598-024-54769-4 -
Nature Communications Nov 2023The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly...
The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.
Topics: Humans; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Microbiota; Metagenome; Bacteria; Neoplasms
PubMed: 37973916
DOI: 10.1038/s41467-023-42997-7 -
Nature Communications Oct 2023Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the... (Meta-Analysis)
Meta-Analysis
Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the contribution of specific bacteria to the risk of severe malaria is unknown. Here, multiomics approaches demonstrate that specific species of Bacteroides are causally linked to the risk of severe malaria. Plasmodium yoelii hyperparasitemia-resistant mice gavaged with murine-isolated Bacteroides fragilis develop P. yoelii hyperparasitemia. Moreover, Bacteroides are significantly more abundant in Ugandan children with severe malarial anemia than with asymptomatic P. falciparum infection. Human isolates of Bacteroides caccae, Bacteroides uniformis, and Bacteroides ovatus were able to cause susceptibility to severe malaria in mice. While monocolonization of germ-free mice with Bacteroides alone is insufficient to cause susceptibility to hyperparasitemia, meta-analysis across multiple studies support a main role for Bacteroides in susceptibility to severe malaria. Approaches that target gut Bacteroides present an opportunity to prevent severe malaria and associated deaths.
Topics: Child; Humans; Animals; Mice; Microbial Consortia; Malaria; Bacteroides; Bacteroides fragilis; Anemia; Plasmodium yoelii
PubMed: 37833304
DOI: 10.1038/s41467-023-42235-0 -
Neoplasia (New York, N.Y.) Sep 2023Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in... (Review)
Review
BACKGROUND
Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in the fecal gut microbiota of patients who are less likely to respond to ICI would be valuable. This systematic review aimed to investigate the association between fecal gut microbiota composition and ICI-treatment response in patients with cancer.
METHODS
EMBASE, Medline, and Cochrane Library databases were searched using the "Participants, Interventions, Comparisons, and Outcomes" (PICO) process to locate studies including participants with solid cancers treated with ICI intervention. The comparator was the gut microbiota, and the outcomes were oncological outcomes such as response rates and progression-free survival. Study data were synthesized qualitatively in a systematic narrative synthesis, and the risk of bias in the studies was assessed.
RESULTS
Two reviewers screened 2092 abstracts independently, and 140 studies were read as full-text reports and assessed for eligibility. Eighteen studies were included with 775 patients with different types of solid cancers who received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Distinct patterns were observed in the patients' fecal samples. Some bacterial species were reported to be present in responders and non-responders, while others were present only in one group. The most reported species associated with better prognosis were Faecalibacterium prausnitzii, Streptococcus parasanguinis, Bacteroides caccae, and Prevotella copri. In contrast, the most reported species associated with poor prognosis were Blautia obeum and Bacteroides ovatus.
CONCLUSION
Distinct microbiota features were associated with good and poor prognoses in ICI-treated patients with cancer.
Topics: Humans; Gastrointestinal Microbiome; Microbiota; Databases, Factual
PubMed: 37603952
DOI: 10.1016/j.neo.2023.100923 -
Nutrients Aug 2023Different research studies have identified specific groups or certain dietary compounds as the onset and progression of obesity and suggested that gut microbiota is a...
Different research studies have identified specific groups or certain dietary compounds as the onset and progression of obesity and suggested that gut microbiota is a mediator between these compounds and the inflammation associated with pathology. In this study, the objective was to evaluate the dietary intake of 108 overweight (OW), obese (OB), and normal-weight (NW) individuals and to analyze their gut microbiota profile to determine changes and associations with Body Mass Index (BMI) and diet. When individuals were compared by BMI, significant differences in fiber and monounsaturated fatty acids (MUFAs) intake were observed, showing higher adequacy for the NW group. The analysis of gut microbiota showed statistical differences for 18 ASVs; and decreased in the OW/OB group, whereas the genus increased; the genus was also found in the LEFSe analysis as a biomarker for OW/OB. was found in a significantly higher proportion of NW individuals and identified as a biomarker for the NW group. Correlation analysis showed that adequation to nutritional recommendation for fiber indicated a higher abundance of , linearly correlated with , , and . The same correlation was found for the adequation for MUFAs, with these bacteria being more abundant when the intake was adjusted to or below the recommendations.
Topics: Humans; Overweight; Gastrointestinal Microbiome; Obesity; Diet; Body Mass Index; Biomarkers
PubMed: 37571355
DOI: 10.3390/nu15153418