AG1, a Novel Synbiotic, Maintains Gut Barrier Function following Inflammatory Challenge in a Caco-2/THP1-Blue™ Co-Culture Model.

Nutritional interventions to reduce gastrointestinal (GI) permeability are of significant interest to physically active adults and those experiencing chronic health conditions. This in vitro study was designed to assess the impact of AG1, a novel synbiotic, on GI permeability following an inflammatory challenge. Interventions [AG1 (vitamins/minerals, pre-/probiotics, and phytonutrients) and control (control medium)] were fed separately into a human GI tract model (stomach, small intestine, and colon).

AG1 Induces a Favorable Impact on Gut Microbial Structure and Functionality in the Simulator of Human Intestinal Microbial Ecosystem Model.

Modulation of the human gut microbiome has become an area of interest in the nutraceutical space. We explored the effect of the novel foundational nutrition supplement AG1 on the composition of human microbiota in an in vitro experimental design. Employing the Simulator of Human Intestinal Microbial Ecosystem (SHIME) model, AG1 underwent digestion, absorption, and subsequent colonic microenvironment simulation under physiologically relevant conditions in healthy human fecal inocula.

Nutrient synergy: definition, evidence, and future directions.

Nutrient synergy refers to the concept that the combined effects of two or more nutrients working together have a greater physiological impact on the body than when each nutrient is consumed individually. While nutrition science traditionally focuses on isolating single nutrients to study their effects, it is recognized that nutrients interact in complex ways, and their combined consumption can lead to additive effects. Additionally, the Dietary Reference Intakes (DRIs) provide guidelines to prevent nutrient deficiencies and excessive intake but are not designed to assess the potential synergistic effects of consuming nutrients together.

Co-consuming green tea with raloxifene decreases raloxifene systemic exposure in healthy adult participants.

Green tea is a popular beverage worldwide. The abundant green tea catechin (-)-epigallocatechin gallate (EGCG) is a potent in vitro inhibitor of intestinal UDP-glucuronosyltransferase (UGT) activity (K  ~2 μM). Co-consuming green tea with intestinal UGT drug substrates, including raloxifene, could increase systemic drug exposure.

Foundational Nutrition: Implications for Human Health.

Human nutrition, and what can be considered "ideal" nutrition, is a complex, multi-faceted topic which many researchers and practitioners deliberate. While some attest that basic human nutrition is relatively understood, it is undeniable that a global nutritional problem persists. Many countries struggle with malnutrition or caloric deficits, while others encounter difficulties with caloric overconsumption and micronutrient deficiencies.

Intestinal Dysbiosis as a component of pathophysiology in succinic semialdehyde dehydrogenase deficiency (SSADHD).

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited inborn error of the γ-aminobutyric acid (GABA) metabolism pathway. It results from mutations in the ALDH5A1 gene leading to elevated GABA, γ-hydroxybutyric acid (GHB), succinic semialdehyde (SSA), decreased glutamine and alterations in several other metabolites. The phenotype includes developmental and cognitive delays, hypotonia, seizures, neuropsychiatric morbidity and other nervous system pathologies.

Microbiome Methods in Experimental Autoimmune Encephalomyelitis.

Microbiome composition studies are increasingly shedding light on animal models of disease. This paper describes a protocol for analyzing the gut microbiome composition prior to and after the induction of mice to experimental autoimmune encephalomyelitis (EAE), the principal animal model of the human neuroinflammatory demyelinating disease multiple sclerosis (MS). We also address and provide data assessing the impact of mice reared in different animal facilities on EAE induction.

Farnesol induces protection against murine CNS inflammatory demyelination and modifies gut microbiome.

Farnesol is a 15‑carbon organic isoprenol synthesized by plants and mammals with anti-oxidant, anti-inflammatory, and neuroprotective activities. We sought to determine whether farnesol treatment would result in protection against murine experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis (MS). We compared disease progression and severity in C57BL/6 mice treated orally with 100 mg/kg/day farnesol solubilized in corn oil to corn-oil treated and untreated EAE mice.

Postmortem Analyses in a Patient With Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): II. Histological, Lipid, and Gene Expression Outcomes in Regional Brain Tissue.

This study has extended previous metabolic measures in postmortem tissues (frontal and parietal lobes, pons, cerebellum, hippocampus, and cerebral cortex) obtained from a 37-year-old male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) who expired from SUDEP (sudden unexplained death in epilepsy). Histopathologic characterization of fixed cortex and hippocampus revealed mild to moderate astrogliosis, especially in white matter. Analysis of total phospholipid mass in all sections of the patient revealed a 61% increase in cortex and 51% decrease in hippocampus as compared to (n = 2-4) approximately age-matched controls.

Dysbiosis of the intestinal microbiome as a component of pathophysiology in the inborn errors of metabolism.

Inborn errors of metabolism (IEMs) represent monogenic disorders in which specific enzyme deficiencies, or a group of enzyme deficiencies (e.g., peroxisomal biogenesis disorders) result in either toxic accumulation of metabolic intermediates or deficiency in the production of key end-products (e.

Novel biomarkers and age-related metabolite correlations in plasma and dried blood spots from patients with succinic semialdehyde dehydrogenase deficiency.

Background: Previous work has identified age-related negative correlations for γ-hydroxybutyric acid (GHB) and γ-aminobutyric acid (GABA) in plasma of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD). Using plasma and dried blood spots (DBS) collected in an ongoing natural history study, we tested the hypothesis that other biomarkers would follow a similar age-related negative correlation as seen for GHB/GABA. Samples (mixed sex) included: patients (n = 21 unique samples, 1-39.

Functional analysis of thirty-four suspected pathogenic missense variants in ALDH5A1 gene associated with succinic semialdehyde dehydrogenase deficiency.

Deficiency of succinate semialdehyde dehydrogenase (SSADH; aldehyde dehydrogenase 5a1 (ALDH5A1), OMIM 271980, 610045), the second enzyme of GABA degradation, represents a rare autosomal-recessively inherited disorder which manifests metabolically as gamma-hydroxybutyric aciduria. The neurological phenotype includes intellectual disability, autism spectrum, epilepsy and sleep and behavior disturbances. Approximately 70 variants have been reported in the ALDH5A1 gene, half of them being missense variants.

Correction to: Post-mortem tissue analyses in a patient with succinic semialdehyde dehydrogenase deficiency (SSADHD). I. Metabolomic outcomes.

Upon publication, it was noted that five of the on-line supplementary figures had incorrect figure: figure legend associations. These were supplementary Figs. 6, 7, 14, 15, and 23.

Post-mortem tissue analyses in a patient with succinic semialdehyde dehydrogenase deficiency (SSADHD). I. Metabolomic outcomes.

Metabolomic characterization of post-mortem tissues (frontal and parietal cortices, pons, cerebellum, hippocampus, cerebral cortex, liver and kidney) derived from a 37 y.o. male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) was performed in conjunction with four parallel series of control tissues.

The Gut Microbiome in Multiple Sclerosis: A Potential Therapeutic Avenue.

Recently, there has been a substantial increase in the number of studies focused upon connecting the gut microbiome with cases of central nervous system (CNS) autoimmunity. Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the CNS. Recent experimental and clinical evidence suggests the presence of microbial imbalances in the gut of MS sufferers.

The Gut Microbiome and Multiple Sclerosis.

The microbiome can be defined as the sum of the microbial and host's genome. Recent information regarding this complex organ suggests that in animal models of multiple sclerosis (MS), the composition of the gut microbiome can be altered, giving rise to both the effector and regulatory phases of central nervous system (CNS) demyelination. Experimental findings during the past decade in animal models of MS have provided clear evidence for the significant role of gut microbes in both the effector and regulatory phase of this condition.

A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis.

The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional.