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Meningeal innate lymphoid cells guide inhibitory neurons in early life.

Microbes and mood: innovative biomarker approaches in depression.

Although the field of psychiatry has made gains in biomarker discovery, our ability to change long-term outcomes remains inadequate. Matching individuals to the best treatment for them is a persistent clinical challenge. Moreover, the development of novel treatments has been hampered in part due to a limited understanding of the biological mechanisms underlying individual differences that contribute to clinical heterogeneity. The gut microbiome has become an area of intensive research in conditions ranging from metabolic disorders to cancer. Innovation in these spaces has led to translational breakthroughs, offering novel microbiome-informed approaches that may improve patient outcomes. In this review we examine how translational microbiome research is poised to advance biomarker discovery in mental health, with a focus on depression.

Outcomes of Acute Mesenteric Ischemia in End-Stage Renal Disease and Predictors of Mortality: A Nationwide Assessment.

Background Acute mesenteric ischemia (AMI) is an uncommon disease caused by obstruction of blood flow to the bowel, which can lead to high mortality rates. End-stage renal disease (ESRD) is another disease commonly seen in the elderly. There are limited data evaluating the relationship between AMI and ESRD, but it has been shown that ESRD patients have a higher risk of mesenteric ischemia than the general population. Methods This retrospective analysis utilized the National Inpatient Sample database for 2016, 2017, and 2018 to identify patients with AMI. Patients were then divided into two groups, AMI with ESRD and AMI only. All-cause in-patient mortality, hospital length of stay (LOS), and total costs were identified. The Student's t-test was used to analyze continuous variables, while Pearson's Chi-square test was used to analyze categorical variables. Results A total of 169,245 patients were identified, with 10,493 (6.2%) having ESRD. The AMI with ESRD group had a significantly higher mortality rate than the AMI-only group (8.5% vs 4.5%). Patients with ESRD had a longer LOS (7.4 days vs 5.3 days; P = 0.00), and higher total hospital cost ($91,520 vs $58,175; P = 0.00) compared to patients without ESRD. Conclusion The study found that patients with ESRD who were diagnosed with AMI had a significantly higher mortality rate, longer hospital stays, and higher hospital costs than patients without ESRD.

Industrial and Ruminant Trans-Fatty Acids-Enriched Diets Differentially Modulate the Microbiome and Fecal Metabolites in C57BL/6 Mice.

Industrially originated trans-fatty acids (I-tFAs), such as elaidic acid (EA), and ruminant trans-fatty acids (R-tFAs), such as trans-palmitoleic acid (TPA), may have opposite effects on metabolic health. The objective was to compare the effects of consuming 2-3% I-tFA or R-tFA on the gut microbiome and fecal metabolite profile in mice after 7 and 28 days. Forty C57BL/6 mice were assigned to one of the four prepared formulations: lecithin nanovesicles, lecithin nanovesicles with EA or TPA, or water. Fecal samples and animals' weights were collected on days 0, 7, and 28. Fecal samples were used to determine gut microbiome profiles by 16S rRNA sequencing and metabolite concentrations by GC/MS. At 28 days, TPA intake decreased the abundance of Staphylococcus sp55 but increased Staphylococcus sp119. EA intake also increased the abundance of Staphylococcus sp119 but decreased Ruminococcaceae UCG-014, Lachnospiraceae, and Clostridium sensu stricto 1 at 28 days. Fecal short-chain fatty acids were increased after TPA while decreased after EA after 7 and 28 days. This study shows that TPA and EA modify the abundance of specific microbial taxa and fecal metabolite profiles in distinct ways.

Organizing principles of astrocytic nanoarchitecture in the mouse cerebral cortex.

Astrocytes are increasingly understood to be important regulators of central nervous system (CNS) function in health and disease; yet, we have little quantitative understanding of their complex architecture. While broad categories of astrocytic structures are known, the discrete building blocks that compose them, along with their geometry and organizing principles, are poorly understood. Quantitative investigation of astrocytic complexity is impeded by the absence of high-resolution datasets and robust computational approaches to analyze these intricate cells. To address this, we produced four ultra-high-resolution datasets of mouse cerebral cortex using serial electron microscopy and developed astrocyte-tailored computer vision methods for accurate structural analysis. We unearthed specific anatomical building blocks, structural motifs, connectivity hubs, and hierarchical organizations of astrocytes. Furthermore, we found that astrocytes interact with discrete clusters of synapses and that astrocytic mitochondria are distributed to lie closer to larger clusters of synapses. Our findings provide a geometrically principled, quantitative understanding of astrocytic nanoarchitecture and point to an unexpected level of complexity in how astrocytes interact with CNS microanatomy.

Microbe-Immune-Stress Interactions Impact Behaviour during Postnatal Development.

Decades of research have established the role of microbiota-brain communication in behaviour and brain function. Studies have shown that microbiota composition and diversity are influenced by a variety of factors including host genetics, diet, and other environmental exposures, with implications for the immunological and neurobiological development of the host organism. To further understand early-life interactions between environment, genetic factors, the microbiome and the central nervous system, we investigated the impact of postnatal stress in C57Bl/6 wild type and T-cell deficient mice on microbe-brain interactions and behaviour. Mice were exposed to immune challenge with lipopolysaccharide (LPS) at postnatal day (P) 3 and maternal separation at P9 (16 h overnight). Behavioural assessment of growth and development as well as behaviour (righting reflex, ultrasonic vocalizations in response to brief maternal separation, open field, sociability, and grooming) was conducted. Microbiota diversity and composition of fecal samples collected at P24 revealed reduced alpha diversity in T-cell-deficient mice as well as genotype- and stress-related taxa. Notably, integrated analyses of microbiota and behaviour in the context of immunocompromise revealed key behavioural related taxa that may be important to brain development. These findings are important to determining the influence of genetic and environmental factors on gut microbiota and advances our understanding microbiome-brain signaling pathways on neurodevelopment and behaviour.

Microbe-Immune Crosstalk: Evidence That T Cells Influence the Development of the Brain Metabolome.

Cross-talk between the immune system and the brain is essential to neuronal development, neuronal excitability, neuroplasticity, and neurotransmission. Gut microbiota are essential to immune system development and immune function; hence, it is essential to consider more broadly the microbiota-immune-brain axis in neurodevelopment. The gut, brain, and microbial metabolomes obtained from C57Bl/6 and T-cell-deficient mice across four developmental timepoints (postnatal day 17, 24, 28, and 84) were studied by 1H NMR spectroscopy. 16S rRNA gene sequencing was performed on cecal and fecal samples. In the absence of T-cells, the developmental trajectory of the gut microbiota and of the host's metabolic profile was altered. The novel insights from this work include (1) the requirement of functional T-cells for the normal trajectory of microbiotal development and the metabolic maturation of the supra-organism, (2) the potential role for Muribaculaceae taxa in modulating the cecal availability of metabolites previously implicated with a role in the gut-brain axis in T-cell deficient mice, and (3) the impact of T-cell-deficiency on central levels of neuroactive metabolites.

Microbial Medicine: Prebiotic and Probiotic Functional Foods to Target Obesity and Metabolic Syndrome.

Obesity has become a global epidemic and a public health crisis in the Western World, experiencing a threefold increase in prevalence since 1975. High-caloric diets and sedentary lifestyles have been identified as significant contributors to this widespread issue, although the role of genetic, social, and environmental factors in obesity's pathogenesis remain incompletely understood. In recent years, much attention has been drawn to the contribution of the gut microbiota in the development of obesity. Indeed, research has shown that in contrast to their healthier counterparts the microbiomes of obese individuals are structurally and functionally distinct, strongly suggesting microbiome as a potential target for obesity therapeutics. In particular, pre and probiotics have emerged as effective and integrative means of modulating the microbiome, in order to reverse the microbial dysbiosis associated with an obese phenotype. The following review brings forth animal and human research supporting the myriad of mechanisms by which the microbiome affects obesity, as well as the strengths and limitations of probiotic or prebiotic supplementation for the prevention and treatment of obesity. Finally, we set forth a roadmap for the comprehensive development of functional food solutions in combatting obesity, to capitalize on the potential of pre/probiotic therapies in optimizing host health.

The Microbiome and Alzheimer's Disease: Potential and Limitations of Prebiotic, Synbiotic, and Probiotic Formulations.

The Microbiome has generated significant attention for its impacts not only on gastrointestinal health, but also on signaling pathways of the enteric and central nervous system via the microbiome gut-brain axis. In light of this, microbiome modulation may be an effective therapeutic strategy for treating or mitigating many somatic and neural pathologies, including neurodegenerative disorders. Alzheimer's disease (AD) is a chronic neurodegenerative disease that interferes with cerebral function by progressively impairing memory, thinking and learning through the continuous depletion of neurons. Although its etiopathogenesis remains uncertain, recent literature endorses the hypothesis that probiotic, prebiotic and synbiotic supplementation alters AD-like symptoms and improves many of its associated disease biomarkers. Alternatively, a dysfunctional microbiota impairs the gut epithelial barrier by inducing chronic gastric inflammation, culminating in neuroinflammation and accelerating AD progression. The findings in this review suggest that probiotics, prebiotics or synbiotics have potential as novel biological prophylactics in treatment of AD, due to their anti-inflammatory and antioxidant properties, their ability to improve cognition and metabolic activity, as well as their capacity of producing essential metabolites for gut and brain barrier permeability.