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Reanalysis of the Mars500 experiment reveals common gut microbiome alterations in astronauts induced by long-duration confinement.

ABSTRACT: Maintaining astronaut health throughout long-duration spaceflight is essential to the feasibility of a manned mission to Mars. The ground-based Mars500 experiment investigated long-duration health by isolating six astronauts for 520 days, the longest controlled human confinement study conducted to date. After 520 days, astronauts had uniform strength and lean body mass losses, and increased fasting plasma glucose, calprotectin, and neutrophil levels characteristic of intestinal inflammation but previous analyses revealed no common significant changes in gut microbiota. This study reanalysed data from early (days 7-45) and late (days 420-520) faecal samples and identified 408 exact sequence variants (ESVs), including 213 shared by all astronauts. Thirty-two ESVs were significantly differentially abundant over time, including depletion of keystone resistant starch degrading, anti-inflammatory and insulin sensitivity-associated species, such as Faecalibacterium prausnitzii, Ruminococcus bromii, Blautia luti, Anaerostipes hadrus, Roseburia faecis, and Lactobacillus rogosae, and enrichment of yet-to-be-cultured bacteria. Additionally, the extraordinary experimental confinement allowed observation of microbiota potentially shared between astronauts and their habitat. Forty-nine species were shared, representing 49% and 12% of the human and environmental microbiome diversity, respectively. These findings reveal the microbiota which significantly altered in relative abundance throughout confinement, including species known to influence inflammation and host glucose homeostasis consistent with astronaut symptoms. Identification of microbiome alterations after 520 days of isolation represents a missing piece connecting Mars500 astronaut physiological studies. Knowledge of the impact of long-term confinement upon the human microbiome helps to improve our understanding of how humans interact with their habitats and is a valuable step forward towards enabling long-duration spaceflight.

SUBMITTER: Brereton NJB

PROVIDER: S-EPMC8099722 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s) have not yet been surveyed in a comprehensive manner. Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing. Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS) revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05) and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension. Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between hypertension and gut microbiota will offer new prospects for treating and preventing the hypertension and its associated diseases.

Project description:Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid intima-media thickening, carotid plaque formation, and carotid stenosis. Accumulating evidence indicates that the gut microbiota plays an important role in CVD and gut-brain disorders, but the associations of the composition and metabolites of the gut microbiome with CAS have not been studied comprehensively. We performed a gut microbiome genome-wide association study in 31 patients with CAS and 51 healthy controls using whole-genome shotgun sequencing. We found that several risk factors (waist circumference, body mass index, diastolic blood pressure, systolic blood pressure, fasting blood glucose, glycated hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein cholesterol) and inflammatory markers (white blood cell count and absolute value of neutrophils) were significantly higher in the CAS group than in the control group. In addition, 21 species and 142 pathways were enriched in the CAS group, and 10 species and 1 pathway were enriched in the control group. Specifically, Bacteroides eggerthii, Escherichia coli, and Klebsiella pneumoniae were the most abundant species in the CAS group, whereas Parabacteroides unclassified, Prevotella copri, Bacteroides sp 3_1_19, and Haemophilus parainfluenzae were the most abundant species in the control group. Finally, we found that most gut microbes and microbial pathways that were enriched in the CAS group had significant positive correlations with clinical characteristics, whereas the microbes and pathways enriched in healthy controls had significant negative correlations with clinical characteristics excluding high-density lipoprotein cholesterol. In addition, the associations between gut microbes and some microbial pathways (short-chain fatty acid, lipopolysaccharide, and menaquinol biosynthesis) were identified. Our results indicate the existence of a cyclic pathway that elevates the circulating concentrations of trimethylamine-N-oxide in patients with CAS but reduces its concentrations in healthy controls.

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Reanalysis of the Mars500 experiment reveals common gut microbiome alterations in astronauts induced by long-duration confinement.

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