scholarly journals Genome-Resolved Metagenomics of the Chicken Gut Microbiome

2021 ◽  
Vol 12 ◽  
Author(s):  
Maia Segura-Wang ◽  
Nikolaus Grabner ◽  
Andreas Koestelbauer ◽  
Viviana Klose ◽  
Mahdi Ghanbari
Keyword(s):  
Gut Microbiome ◽  
Animal Health ◽  
Short Chain Fatty Acids ◽  
Major Effect ◽  
Glycoside Hydrolases ◽  
Metagenomic Sequencing ◽  
Gastrointestinal Microbiota ◽  
Metabolic Potential ◽  
Host Microbe Interactions ◽  
Chicken Gut Microbiota

Increasing evidence shows that the chicken gastrointestinal microbiota has a major effect on the modulation of metabolic functions and is correlated with economic parameters, such as feed efficiency and health. Some of these effects derive from the capacity of the chicken to digest carbohydrates and produce energy-rich metabolites such as short-chain fatty acids (SCFA) and from host-microbe interactions. In this study, we utilized information from metagenomic assembled genomes (MAGs) from chicken gastrointestinal tract (GIT) samples, with detailed annotation of carbohydrate-active enzymes (CAZymes) and genes involved in SCFA production, to better understand metabolic potential at different ages. Metagenomic sequencing of 751 chicken GIT samples was performed to reconstruct 155 MAGs, representing species which belong to six phyla, primarily Firmicutes followed by Proteobacteria. MAG diversity significantly (p < 0.001) increased with age, with early domination of Lachnospiraceae, followed by other families including Oscillospiraceae. Age-dependent shifts were observed in the abundance of genes involved in CAZyme and SCFA production, exemplified by a significant increase in glycosyltransferases (GTs) and propionic acid production pathways (p < 0.05), and a lower abundance of glycoside hydrolases (GHs) (p < 0.01). Co-occurrence analysis revealed a large cluster highly interconnected by enzymes from GT2_2 and GH3 families, underscoring their importance in the community. Furthermore, several species were identified as interaction hubs, elucidating associations of key microbes and enzymes that more likely drive temporal changes in the chicken gut microbiota, and providing further insights into the structure of the complex microbial community. This study extends prior efforts on the characterization of the chicken GIT microbiome at the taxonomic and functional levels and lays an important foundation toward better understanding the broiler chicken gut microbiome helping in the identification of modulation opportunities to increase animal health and performance.

scholarly journals Glucocorticoids modulate gastrointestinal microbiome in a wild bird

2018 ◽  
Vol 5 (4) ◽  
pp. 171743 ◽  
Author(s):  
José C. Noguera ◽  
Manuel Aira ◽  
Marcos Pérez-Losada ◽  
Jorge Domínguez ◽  
Alberto Velando
Keyword(s):  
Gut Microbiome ◽  
Animal Health ◽  
Natural Populations ◽  
Risk Of Infection ◽  
Stress Exposure ◽  
Gastrointestinal Microbiota ◽  
Gastrointestinal Microbiome ◽  
Close Link ◽  
Future Studies ◽  
Larus Michahellis

It has recently been hypothesized that stress exposure (e.g. via glucocorticoid secretion) may dysregulate the bacterial gut microbiome, a crucial ‘organ' in animal health. However, whether stress exposure (e.g. via glucocorticoid secretion) affects the bacterial gut microbiome of natural populations is unknown. We have experimentally altered the basal glucocorticoid level (corticosterone implants) in a wild avian species, the yellow-legged gull Larus michahellis , to assess its effects on the gastrointestinal microbiota. Our results suggest underrepresentation of several microbial taxa in the corticosterone-implanted birds. Importantly, such reduction included potentially pathogenic avian bacteria (e.g. Mycoplasma and Microvirga ) and also some commensal taxa that may be beneficial for birds (e.g. Firmicutes). Our findings clearly demonstrate a close link between microbiome communities and glucocorticoid levels in natural populations. Furthermore, they suggest a beneficial effect of stress in reducing the risk of infection that should be explored in future studies.

scholarly journals Interplay between the human gut microbiome and host metabolism

2019 ◽  
Author(s):  
Alessia Visconti ◽  
Caroline I. Le Roy ◽  
Fabio Rosa ◽  
Niccolo Rossi ◽  
Tiphaine C. Martin ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Taxonomic Composition ◽  
Metagenomic Sequencing ◽  
Human Gut ◽  
Metabolic Potential ◽  
Microbial Ecosystem ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing ◽  
Key Species

AbstractThe human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.

Metagenomic profiling of gut microbiome in early chronic kidney disease

2020 ◽  
Author(s):  
Noriaki Sato ◽  
Masanori Kakuta ◽  
Takanori Hasegawa ◽  
Rui Yamaguchi ◽  
Eiichiro Uchino ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Toxin Production ◽  
Metagenomic Sequencing ◽  
Stool Samples ◽  
The Mean ◽  
Estimated Glomerular Filtration Rates ◽  
The Relationship

Abstract Background The relationship between chronic kidney disease (CKD) and the gut microbiome, which interact through chronic inflammation, uraemic toxin production and immune response regulation, has gained interest in the development of CKD therapies. However, reports using shotgun metagenomic analysis of the gut microbiome are scarce, especially for early CKD. Here we characterized gut microbiome differences between non-CKD participants and ones with early CKD using metagenomic sequencing. Methods In total, 74 non-CKD participants and 37 participants with early CKD were included based on propensity score matching, controlling for various factors including dietary intake. Stool samples were collected from participants and subjected to shotgun sequencing. Bacterial and pathway abundances were profiled at the species level with MetaPhlAn2 and HUMAnN2, respectively, and overall microbiome differences were determined using Bray–Curtis dissimilarities. Diabetic and non-diabetic populations were analysed separately. Results For diabetic and non-diabetic participants, the mean estimated glomerular filtration rates of the CKD group were 53.71 [standard deviation (SD) 3.87] and 53.72 (SD 4.44), whereas those of the non-CKD group were 72.63 (SD 7.72) and 76.10 (SD 9.84), respectively. Alpha and beta diversities were not significantly different between groups. Based on taxonomic analysis, butyrate-producing species Roseburia inulinivorans, Ruminococcus torques and Ruminococcus lactaris were more abundant in the non-CKD group, whereas Bacteroides caccae and Bacteroides coprocora were more abundant in the non-diabetic CKD group. Conclusions Although gut microbiome changes in individuals with early CKD were subtle, the results suggest that changes related to producing short-chain fatty acids can already be observed in early CKD.

scholarly journals Metagenomic insights into the diversity of carbohydrate-degrading enzymes in the yak fecal microbial community

2020 ◽  
Author(s):  
Ga Gong ◽  
Saisai Zhou ◽  
Runbo Luo ◽  
Zhuoma Gesang ◽  
Sizhu Suolang
Keyword(s):  
Microbial Community ◽  
Intestinal Flora ◽  
Glycoside Hydrolases ◽  
Limited Information ◽  
Gastrointestinal Microbiota ◽  
Metabolic Potential ◽  
Plant Materials ◽  
Fecal Microbiome ◽  
Degrading Enzymes ◽  
Wide Range

Abstract Background: As a special herbivorous ruminant, yak is supposed to utilize the gastrointestinal microbiota to digest plant materials. Although the cellulolytic bacteria of yak rumen have been reported, there is still limited information about whether carbohydrate metabolizing enzymes in its intestinal flora are abundant for the degradation of complex lignocellulosic biomass. Results: Here, this study aimed to decode the structure and function of yak fecal microbiota using deep metagenome sequencing. A comprehensive gene catalog comprising 4.5 million microbial genes was established and functionally annotated to characterize the primary metabolic potential of the microbiome based on metagenomic assemblies from 92 Gb sequencing data. A full spectrum of genes encoding carbohydrate-active enzymes were identified and about three-quarters of these genes assigned to a wide range of enzyme families were involved in the breakdown of complex dietary carbohydrates, including 120 families of glycoside hydrolases, 25 families of polysaccharide lyases, and 15 families of carbohydrate esterases. Inference of taxonomic assignments to the carbohydrate-degrading enzymes revealed the major microbial contributors were the members of Firmicutes and Bacteroidetes, both of which were also the most dominating bacterial populations in the yak fecal microbiome. Metagenomic binning further reconstructed 86 prokaryotic genomes, and a highly diversified profile of glycoside hydrolases associated with plant-derived polysaccharide degradation was also identified in these uncultured genomes, many of which were novel species with highly fibrolytic capability. Conclusions: Our findings shed light on a great diversity of carbohydrate-degrading enzymes in the yak gut microbial community and uncultured species, providing a useful genetic resource for future studies on the discovery of novel enzymes with industrial potential.

scholarly journals Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice

mSystems ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Thomas Sharpton ◽  
Svetlana Lyalina ◽  
Julie Luong ◽  
Joey Pham ◽  
Emily M. Deal ◽  
...  
Keyword(s):  
Mouse Model ◽  
Microbial Communities ◽  
Immune Activation ◽  
Gut Microbiome ◽  
Longitudinal Design ◽  
Disease Onset ◽  
Mixed Effects ◽  
Metagenomic Sequencing ◽  
Early Biomarkers ◽  
Host Microbe Interactions

ABSTRACT IBD patients harbor distinct microbial communities with functional capabilities different from those seen with healthy people. But is this cause or effect? Answering this question requires data on changes in gut microbial communities leading to disease onset. By performing weekly metagenomic sequencing and mixed-effects modeling on an established mouse model of IBD, we identified several functional pathways encoded by the gut microbiome that covary with host immune status. These pathways are novel early biomarkers that may either enable microbes to live inside an inflamed gut or contribute to immune activation in IBD mice. Future work will validate the potential roles of these microbial pathways in host-microbe interactions and human disease. This study was novel in its longitudinal design and focus on microbial pathways, which provided new mechanistic insights into the role of gut microbes in IBD development. The gut microbiome is linked to inflammatory bowel disease (IBD) severity and altered in late-stage disease. However, it is unclear how gut microbial communities change over the course of IBD development, especially in regard to function. To investigate microbiome-mediated disease mechanisms and discover early biomarkers of IBD, we conducted a longitudinal metagenomic investigation in an established mouse model of IBD, where damped transforming growth factor β (TGF-β) signaling in T cells leads to peripheral immune activation, weight loss, and severe colitis. IBD development is associated with abnormal gut microbiome temporal dynamics, including damped acquisition of functional diversity and significant differences in abundance trajectories for KEGG modules such as glycosaminoglycan degradation, cellular chemotaxis, and type III and IV secretion systems. Most differences between sick and control mice emerge when mice begin to lose weight and heightened T cell activation is detected in peripheral blood. However, levels of lipooligosaccharide transporter abundance diverge prior to immune activation, indicating that it could be a predisease indicator or microbiome-mediated disease mechanism. Taxonomic structure of the gut microbiome also significantly changes in association with IBD development, and the abundances of particular taxa, including several species of Bacteroides, correlate with immune activation. These discoveries were enabled by our use of generalized linear mixed-effects models to test for differences in longitudinal profiles between healthy and diseased mice while accounting for the distributions of taxon and gene counts in metagenomic data. These findings demonstrate that longitudinal metagenomics is useful for discovering the potential mechanisms through which the gut microbiome becomes altered in IBD. IMPORTANCE IBD patients harbor distinct microbial communities with functional capabilities different from those seen with healthy people. But is this cause or effect? Answering this question requires data on changes in gut microbial communities leading to disease onset. By performing weekly metagenomic sequencing and mixed-effects modeling on an established mouse model of IBD, we identified several functional pathways encoded by the gut microbiome that covary with host immune status. These pathways are novel early biomarkers that may either enable microbes to live inside an inflamed gut or contribute to immune activation in IBD mice. Future work will validate the potential roles of these microbial pathways in host-microbe interactions and human disease. This study was novel in its longitudinal design and focus on microbial pathways, which provided new mechanistic insights into the role of gut microbes in IBD development.

scholarly journals The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis

2015 ◽  
Vol 309 (10) ◽  
pp. E840-E851 ◽  
Author(s):  
Miles Fuller ◽  
Medha Priyadarshini ◽  
Sean M. Gibbons ◽  
Anthony R. Angueira ◽  
Michael Brodsky ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Homeostasis ◽  
Gut Microbiome ◽  
Cell Mass ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Functional Difference ◽  
Gastrointestinal Microbiota ◽  
Acid Receptor ◽  
Fatty Acid Receptor

The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene ( Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2−/− mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2−/− and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2−/− mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.

Associations between gut microbiome, short chain fatty acids and blood pressure across ethnic groups: the HELIUS study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Verhaar ◽  
D Collard ◽  
A Prodan ◽  
J.H.M Levels ◽  
A.H Zwinderman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Ethnic Groups ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Funding Source ◽  
Microbiome Composition ◽  
Helius Study ◽  
Chain Fatty Acids

Abstract Background Gut microbiome composition is shaped by a combination of host genetic make-up and dietary habits. In addition, large ethnic differences exist in microbiome composition. Several studies in humans and animals have shown that differences in gut microbiota and its metabolites, including short chain fatty acids (SCFA), are associated with blood pressure (BP). We hypothesized that gut microbiome composition and its metabolites may be differently associated with BP across ethnic groups. Purpose To investigate associations of gut microbiome composition and fecal SCFA levels with BP across different ethnic groups. Methods We assessed the association between gut microbiome composition and office BP among 4672 subjects (mean age 49.8±11.7 years, 52%F) of 6 different ethnic groups participating in the HELIUS study. Gut microbiome composition was determined using 16S rRNA sequencing. Associations between microbiome composition and blood pressure were assessed using machine learning prediction models. The resulting best predictors were correlated with BP using Spearman's rank correlations. Fecal SCFA levels were measured with high-performance liquid chromatography in an age- and body mass index (BMI)-matched subgroup of 200 participants with either extreme low or high systolic BP. Differences in abundances of best predictors and fecal SCFA levels between high and low BP groups were assessed with Mann-Whitney U tests. Results Gut microbiome composition explained 4.4% of systolic BP variance. Best predictors for systolic BP included Roseburia spp. (ρ −0.15, p<0.001), Clostridium spp. (ρ −0.14, p<0.001), Romboutsia spp. (ρ −0.10, p<0.001), and Ruminococceae spp. (ρ −0.15, p<0.001) (Figure 1). Explained variance of the microbiome composition was highest in Dutch subjects (4.8%), but very low in African Surinamese, Ghanaian, and Turkish ethnic groups (ranging from 0–0.77%) Hence, we selected only participants with Dutch ethnicity for the matched subgroup. Participants with high BP had lower abundance of Roseburia hominis (p<0.01) and Roseburia spp. (p<0.05) compared to participants with low BP. However, fecal acetate (p<0.05) and propionate (p<0.01) levels were higher in participants with high BP. Conclusions In this cross-sectional study, gut microbiome composition was moderately associated with BP. Associations were strongly divergent between ethnic groups, with strongest associations in Dutch participants. Intriguingly, while Dutch participants with high BP had lower abundances of several SCFA-producing microbes, they had higher fecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD Amsterdam) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation (Hartstichting; grant no. 2010T084), the Netherlands Organization for Health Research and Development (ZonMw; grant no. 200500003), the European Integration Fund (EIF; grant no. 2013EIF013) and the European Union (Seventh Framework Programme, FP-7; grant no. 278901).

Gut microbiome–short-chain fatty acids interplay in the context of iron deficiency anaemia

2021 ◽  
Author(s):  
Ana Soriano-Lerma ◽  
María García-Burgos ◽  
María J.M. Alférez ◽  
Virginia Pérez-Carrasco ◽  
Victoria Sanchez-Martin ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Iron Deficiency ◽  
Gut Microbiome ◽  
Iron Deficiency Anaemia ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Deficiency Anaemia ◽  
Chain Fatty Acids

scholarly journals 673 Precision microbiome mapping identifies a microbiome signature predictive of Immune checkpoint inhibitor response across multiple research study cohorts

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A711-A711
Author(s):  
Matthew Robinson ◽  
Kevin Vervier ◽  
Simon Harris ◽  
David Adams ◽  
Doreen Milne ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Advanced Melanoma ◽  
List Type ◽  
Metagenomic Sequencing ◽  
Genome Database ◽  
Sequencing Platform ◽  
Melanoma Patients

BackgroundThe gut microbiome of cancer patients appears to be associated with response to Immune Checkpoint Inhibitor (ICIs) treatment.1–4 However, the bacteria linked to response differ between published studies.MethodsLongitudinal stool samples were collected from 69 patients with advanced melanoma receiving approved ICIs in the Cambridge (UK) MELRESIST study. Pretreatment samples were analysed by Microbiotica, using shotgun metagenomic sequencing. Microbiotica’s sequencing platform comprises the world’s leading Reference Genome Database and advanced Microbiome Bioinformatics to give the most comprehensive and precise mapping of the gut microbiome. This has enabled us to identify gut bacteria associated with ICI response missed using public reference genomes. Published microbiome studies in advanced melanoma,1–3renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC)4 were reanalysed with the same platform.ResultsAnalysis of the MELRESIST samples showed an overall change in the microbiome composition between advanced melanoma patients and a panel of healthy donor samples, but not between patients who subsequently responded or did not respond to ICIs. However, we did identify a discrete microbiome signature which correlated with response. This signature predicted response with an accuracy of 93% in the MELRESIST cohort, but was less predictive in the published melanoma cohorts.1–3 Therefore, we developed a bioinformatic analytical model, incorporating an interactive random forest model and the MELRESIST dataset, to identify a microbiome signature which was consistent across all published melanoma studies. This model was validated three times by accurately predicting the outcome of an independent cohort. A final microbiome signature was defined using the validated model on MELRESIST and the three published melanoma cohorts. This was very accurate at predicting response in all four studies combined (91%), or individually (82–100%). This signature was also predictive of response in a NSCLC study and to a lesser extent in RCC. The core of this signature is nine bacteria significantly increased in abundance in responders.ConclusionsAnalysis of the MELRESIST study samples, precision microbiome profiling by the Microbiotica Platform and a validated bioinformatic analysis, have enabled us to identify a unique microbiome signature predictive of response to ICI therapy in four independent melanoma studies. This removes the challenge to the field of different bacteria apparently being associated with response in different studies, and could represent a new microbiome biomarker with clinical application. Nine core bacteria may be driving response and hold potential for co-therapy with ICIs.Ethics ApprovalThe study was approved by Newcastle & North Tyneside 2 Research Ethics Committee, approval number 11/NE/0312.ReferencesMatson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 2018;359(6371):104–108.Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018;359(6371):97–103.Frankel AE, Coughlin LA, Kim J, et al. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia 2017;19(10):848–855.Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018;359(6371):91–97.

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

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