Associations between fecal short-chain fatty acids and sleep continuity in older adults with insomnia symptoms. Magzal Faiga,Even Carmel,Haimov Iris,Agmon Maayan,Asraf Kfir,Shochat Tamar,Tamir Snait Scientific reports Insomnia is a disorder characterized by difficulty falling asleep and poor sleep continuity and is associated with increased risks for physical and cognitive decline. Insomnia with short sleep duration is considered the most biologically severe phenotype of the disorder. Evidence suggests that short-chain fatty acids (SCFAs), the main byproducts of fiber fermentation in the gut, may affect sleep via gut-brain communications. This study explores associations between SCFAs and sleep continuity and compares SCFA concentrations in short vs. normal sleep insomnia phenotypes in older adults. Fifty-nine participants with insomnia symptoms (≥ 65 years), completed 2 weeks of objective sleep monitoring (actigraphy), and were divided into short and normal sleep duration phenotypes via cluster analysis. Sleep measures included total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), and wake after sleep onset (WASO). Stool samples were collected and fecal SCFA concentrations were determined by gas-chromatography-mass-spectrometry (GCMS). Higher concentrations of acetate, butyrate, and propionate, and total SCFAs, were associated with lower SE and longer SOL after controlling for Body Mass Index (BMI). Concentrations were higher in the short sleep duration phenotype. Age, BMI, TST, and SOL explained 40.7% of the variance in total SCFAs. Findings contribute to understanding pathways along the gut-brain axis and may lead to the use of SCFAs as biomarkers of insomnia phenotypes. 10.1038/s41598-021-83389-5

Multiomics Analysis Reveals Aberrant Metabolism and Immunity Linked Gut Microbiota with Insomnia. Microbiology spectrum Studies have confirmed that insomnia is related to gut microbiota. Previous research suggests that immunity and metabolism are also associated with insomnia. However, to our knowledge, the integration of these factors has not been investigated in insomnia. Here, we explored the correlations across gut microbiota, serum metabolism, and inflammatory factors in insomnia. Our results showed that the composition and structure of gut microbiota and metabolism in insomnia patients were different from healthy controls. Compared to healthy controls, the relative abundances of , Streptococcus, and Lactobacillus crispatus were significantly increased in insomniacs. There were five metabolic pathways in insomniacs (glycerophospholipid metabolism; glutathione metabolism; nitrogen metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis) significantly different between the two groups. Moreover, we found that IL-1β levels were significantly higher in insomnia patients while TNF-α was significantly reduced. We further identified that the changes in the level of IL-1β and TNF-α were associated with some specific bacteria and metabolites, such as Prevotella amnii, Prevotella buccalis, Prevotella timonensis, and Prevotella colorans. Mediation analysis further determined that the immune factors and metabolites could mediate the relationship between gut microbes and insomnia. Our study indicated that systematic inflammation and metabolites might be a pathway linking the gut microbiome with insomnia. These findings provide new insights and a better understanding of gut microbiota's role in insomnia as well as potential novel microbiome-related etiologies for insomnia. 10.1128/spectrum.00998-22

Mapping the early life gut microbiome in neonates with critical congenital heart disease: multiomics insights and implications for host metabolic and immunological health. Microbiome BACKGROUND:The early life gut microbiome is crucial in maintaining host metabolic and immune homeostasis. Though neonates with critical congenital heart disease (CCHD) are at substantial risks of malnutrition and immune imbalance, the microbial links to CCHD pathophysiology remain poorly understood. In this study, we aimed to investigate the gut microbiome in neonates with CCHD in association with metabolomic traits. Moreover, we explored the clinical implications of the host-microbe interactions in CCHD. METHODS:Deep metagenomic sequencing and metabolomic profiling of paired fecal samples from 45 neonates with CCHD and 50 healthy controls were performed. The characteristics of gut microbiome were investigated in three dimensions (microbial abundance, functionality, and genetic variation). An in-depth analysis of gut virome was conducted to elucidate the ecological interaction between gut viral and bacterial communities. Correlations between multilevel microbial features and fecal metabolites were determined using integrated association analysis. Finally, we conducted a subgroup analysis to examine whether the interactions between gut microbiota and metabolites could mediate inflammatory responses and poor surgical prognosis. RESULTS:Gut microbiota dysbiosis was observed in neonates with CCHD, characterized by the depletion of Bifidobacterium and overgrowth of Enterococcus, which was highly correlated with metabolomic perturbations. Genetic variations of Bifidobacterium and Enterococcus orchestrate the metabolomic perturbations in CCHD. A temperate core virome represented by Siphoviridae was identified to be implicated in shaping the gut bacterial composition by modifying microbial adaptation. The overgrowth of Enterococcus was correlated with systemic inflammation and poor surgical prognosis in subgroup analysis. Mediation analysis indicated that the overgrowth of Enterococcus could mediate gut barrier impairment and inflammatory responses in CCHD. CONCLUSIONS:We demonstrate for the first time that an aberrant gut microbiome associated with metabolomic perturbations is implicated in immune imbalance and adverse clinical outcomes in neonates with CCHD. Our data support the importance of reconstituting optimal gut microbiome in maintaining host metabolic and immunological homeostasis in CCHD. Video Abstract. 10.1186/s40168-022-01437-2