Gut permeability among Astronauts during Space missions.

The space environment poses substantial challenges to human physiology, including potential disruptions in gastrointestinal health. Gut permeability has only recently become widely acknowledged for its potential to cause adverse effects on a systemic level, rendering it a critical factor to investigate in the context of spaceflight. Here, we propose that astronauts experience the onset of leaky gut during space missions supported by transcriptomic and metagenomic analysis of human and murine samples. A genetic map contributing to intestinal permeability was constructed from a systematic review of current literature. This was referenced against our re-analysis of three independent transcriptomic datasets which revealed significant changes in gene expression patterns associated with the gut barrier. Specifically, in astronauts during flight, we observed a substantial reduction in the expression genes that are crucial for intestinal barrier function, goblet cell development, gut microbiota modulation, and immune responses. Among rodent spaceflight studies, differential expression of cytokines, chemokines, and genes which regulate mucin production and post-translational modifications suggest a similar dysfunction of intestinal permeability. Metagenomic analysis of feces from two murine studies revealed a notable reduction probiotic, short chain fatty acid-producing bacteria and an increase in the Gram-negative pathogens, including Citrobacter rodentium, Enterobacter cloacea, Klebsiella aerogenes, and Proteus hauseri which promote LPS circulation, a recipe for barrier disruption and systemic inflammatory activation. These findings emphasize the critical need to understand the underlying mechanisms and develop interventions to maintain gastrointestinal health in space.

Association between Dysbiosis in the Gut Microbiota of Primary Osteoporosis Patients and Bone Loss.

In recent decades, gut microbiome research has experienced significant growth, driven by technological advances that enable quantifying bacterial taxa with greater precision. Age, diet, and living environment have emerged as three key factors influencing gut microbes. Dysbiosis, resulting from alterations in these factors, may lead to changes in bacterial metabolites that regulate pro- and anti-inflammatory processes and consequently impact bone health. Restoration of a healthy microbiome signature could mitigate inflammation and potentially reduce bone loss associated with osteoporosis or experienced by astronauts during spaceflight. However, current research is hindered by contradictory findings, insufficient sample sizes, and inconsistency in experimental conditions and controls. Despite progress in sequencing technology, defining a healthy gut microbiome across global populations remains elusive. Challenges persist in identifying accurate gut bacterial metabolics, specific taxa, and their effects on host physiology. We suggest greater attention be directed towards this issue in Western countries as the cost of treating osteoporosis in the United States reaches billions of dollars annually, with expenses projected to continue rising.

Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.

Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens Clostridium sensu stricto, Bacteroides, and Intestinibacter was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera Collinsella, Megasphaera, Agathobaculum, Mediterraneibacter, Clostridium XIV, and Dorea, were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including Limosilactobacillus, were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. IMPORTANCE Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.