Randomised control trial indicates micronutrient supplementation may support a more robust maternal microbiome for women with antenatal depression during pregnancy.

Background And Aims: We investigated the effects of high dose dietary micronutrient supplementation or placebo on the human gut microbiome in pregnant women who had moderate symptoms of antenatal depression. There is a significant absence of well-controlled clinical studies that have investigated the dynamic changes of the microbiome during pregnancy and the relationship among diet, microbiome and antenatal depression. This research is among the first to provide an insight into this area of research.

Gestational administration of Bifidobacterium dentium results in intergenerational modulation of inflammatory, metabolic, and social behavior.

Prenatal stress (PNS) profoundly impacts maternal and offspring health, with enduring effects including microbiome alterations, neuroinflammation, and behavioral disturbances such as reductions in social behavior. Converging lines of evidence from preclinical and clinical studies suggest that PNS disrupts tryptophan (Trp) metabolic pathways and reduces gut Bifidobacteria, a known beneficial bacterial genus that metabolizes Trp. Specifically, previous work from our lab demonstrated that human prenatal mood disorders in mothers are associated with reduced Bifidobacterium dentium in infants at 13 months.

Stress and depression-associated shifts in gut microbiota: A pilot study of human pregnancy.

Background: Psychosocial stress and mood-related disorders, such as depression, are prevalent and vulnerability to these conditions is heightened during pregnancy. Psychosocial stress induces consequences via several mechanisms including the gut microbiota-brain axis and associated signaling pathways. Previous preclinical work indicates that prenatal stress alters maternal gut microbial composition and impairs offspring development.

Fetal CCL2 signaling mediates offspring social behavior and recapitulates effects of prenatal stress.

Maternal stress during pregnancy is prevalent and associated with increased risk of neurodevelopmental disorders in the offspring. Maternal and offspring immune dysfunction has been implicated as a potential mechanism by which prenatal stress shapes offspring neurodevelopment; however, the impact of prenatal stress on the developing immune system has yet to be elucidated. Furthermore, there is evidence that the chemokine C-C motif chemokine ligand 2 (CCL2) plays a key role in mediating the behavioral sequelae of prenatal stress.

Discrete role for maternal stress and gut microbes in shaping maternal and offspring immunity.

Psychosocial stress is prevalent during pregnancy, and is associated with immune dysfunction, both for the mother and the child. The gut microbiome has been implicated as a potential mechanism by which stress during pregnancy can impact both maternal and offspring immune function; however, the complex interplay between the gut microbiome and the immune system is not well-understood. Here, we leverage a model of antimicrobial-mediated gut microbiome reduction, in combination with a well-established model of maternal restraint stress, to investigate the independent effects of and interaction between maternal stress and the gut microbiome in shaping maternal and offspring immunity.

Maternal anxiety, depression and stress affects offspring gut microbiome diversity and bifidobacterial abundances.

Uncovering mechanisms underlying fetal programming during pregnancy is of critical importance. Atypical neurodevelopment during the pre- and immediate postnatal period has been associated with long-term adverse health outcomes, including mood disorders and aberrant cognitive ability in offspring. Maternal factors that have been implicated in anomalous offspring development include maternal inflammation and tress, anxiety, and depression.

Associations Between Gut Microbes and Social Behavior in Healthy 2-Year-Old Children.

Objective: Emerging research has connected abundances of specific bacteria to differences in psychosocial behaviors in animals and adult humans. However, research assessing mind-microbiome associations in children is sparse with extant work primarily focused on populations with autism, making it unclear whether links are also present in typically developing children. The current study fills this gap by examining associations between prosocial-self-regulating temperaments (effortful control; EC) and the gut microbiome in typically developing children.

in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats.

Necrotizing enterocolitis (NEC) is a devastating disease affecting premature newborns with no known cure. Up to half of survivors subsequently exhibit cognitive impairment and neurodevelopmental defects. We created a novel probiotics delivery system in which the probiotic () was induced to form a biofilm [ (biofilm)] by incubation with dextranomer microspheres loaded with maltose (-DM-maltose).

Prenatal stress-induced disruptions in microbial and host tryptophan metabolism and transport.

The aromatic amino acid tryptophan (Trp) is a precursor for multiple metabolites that can steer proper immune and neurodevelopment as well as social behavior in later life. Dysregulation in the Trp metabolic pathways and abundance of Trp or its derivatives, including indoles, kynurenine (Kyn), and particularly serotonin, has been associated with behavioral deficits and neuropsychiatric disorders including autism spectrum disorders (ASD) and schizophrenia. Previously, we have shown that prenatal stress (PNS) alters placental Trp and serotonin, and reduces Trp-metabolizing members of the maternal colonic microbiota.

Urine-derived extracellular vesicle miRNAs as possible biomarkers for and mediators of necrotizing enterocolitis: A proof of concept study.

Background: Early-stage symptomology of necrotizing enterocolitis (NEC) is similar in presentation to non-NEC sepsis, though the treatment plans differ based on antibiotic administration and withholding of feeds. Improved diagnostics for NEC differentiation would allow clinicians to more rapidly set individual patients on a targeted treatment path. Extracellular vesicle-derived miRNAs, have previously demonstrated efficacy as disease biomarkers.

Unique maternal immune and functional microbial profiles during prenatal stress.

Maternal stress during pregnancy is widespread and is associated with poor offspring outcomes, including long-term mental health issues. Prenatal stress-induced fetal neuroinflammation is thought to underlie aberrant neurodevelopment and to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent immune and microbial metagenome profiles of stressed gestating mice that may trigger detrimental inflammatory signaling at the maternal-fetal interface.

A novel probiotic therapeutic in a murine model of colitis.

For prophylactic therapy, mice received an oral antibiotic cocktail followed by clindamycin injection, followed by probiotic administration (planktonic . biofilm state), followed by oral gavage. For treatment therapy, mice received antibiotics and first, followed by probiotic administration.

The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles.

In the past few decades, interest in the therapeutic benefits of exosomes and extracellular vesicles (EVs) has grown exponentially. Exosomes/EVs are small particles which are produced and exocytosed by cells throughout the body. They are loaded with active regulatory and stimulatory molecules from the parent cell including miRNAs and enzymes, making them prime targets in therapeutics and diagnostics.

Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis.

Purpose: Necrotizing enterocolitis (NEC) is a leading cause of death in premature infants. Breast feeding decreases the incidence of NEC but, even with aggressive promotion of nursing in Neonatal Intensive Care Units, morbidity and mortality remain high. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) purified from mouse and rat stem cells can protect the intestines from NEC.

Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation.

There is a groundswell of interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we computationally identify the first biological thiosulfate sensor and an improved tetrathionate sensor, both two-component systems from marine species, and validate them in laboratory Then, we port these sensors into a gut-adapted probiotic strain, and develop a method based upon oral gavage and flow cytometry of colon and fecal samples to demonstrate that colon inflammation (colitis) activates the thiosulfate sensor in mice harboring native gut microbiota. Our thiosulfate sensor may have applications in bacterial diagnostics or therapeutics.

Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice.

Stressor exposure significantly affects the colonic mucosa-associated microbiota, and exacerbates Citrobacter rodentium-induced inflammation, effects that can be attenuated with probiotic Lactobacillus reuteri. This study assessed the structure of the colonic mucosa-associated microbiota in mice exposed to a social stressor (called social disruption), as well as non-stressed control mice, during challenge with the colonic pathogen C. rodentium.

The commensal microbiota exacerbate infectious colitis in stressor-exposed mice.

Exposure to a prolonged restraint stressor disrupts the colonic microbiota community composition, and is associated with an elevated inflammatory response to colonic pathogen challenge. Since the stability of the microbiota has been implicated in the development and modulation of mucosal immune responses, we hypothesized that the disruptive effect of the stressor upon the microbiota composition directly contributed to the stressor-induced exacerbation of pathogen-induced colitis. In order to establish a causative role for stressor-induced changes in the microbiota, conventional mice were exposed to prolonged restraint to change the microbiota.

The Impact of Dietary Energy Intake Early in Life on the Colonic Microbiota of Adult Mice.

The complex and dynamic interactions between diet, gut microbiota (GM) structure and function, and colon carcinogenesis are only beginning to be elucidated. We examined the colonic microbiota and aberrant crypt foci (ACF) in C57BL/6N female mice fed various dietary interventions (control, energy restricted and high-fat) provided during two phases (initiation and progression) of azoxymethane (AOM)-induced early colon carcinogenesis. During progression (wks.

The prebiotics 3'Sialyllactose and 6'Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis.

There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3'Sialyllactose (3'SL) or 6'Sialyllactose (6'SL) for 2 weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition.

A Comparison of Zirconia and Titanium Abutments for Microleakage.

Background: Microleakage through the interface has been documented in implant systems with titanium (Ti) abutments. There is a current increase in the use of zirconia (Zi) abutments especially in esthetic zone in where higher risk of visible metal color through the peri-implant tissues exists.

Purpose: The aim of the present in vitro study is to evaluate the leakage at the implant fixture-abutment interface with two different screw-retained abutment systems at different torque values in a nonloading condition.

Intestinal microbial dysbiosis and colonic epithelial cell hyperproliferation by dietary α-mangostin is independent of mouse strain.

Beverages and supplements prepared from mangosteen fruit are claimed to support gut health and immunity, despite the absence of supporting evidence from clinical trials. We recently reported that α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, altered the intestinal microbiome, promoted dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study was to determine whether induction of dysbiosis by dietary α-MG is limited to the C57BL/6J strain or represents a more generic response to chronic intake of the xanthone on the gut microbiota of mice.

The structures of the colonic mucosa-associated and luminal microbial communities are distinct and differentially affected by a prolonged murine stressor.

The commensal microbiota of the human gastrointestinal tract live in a largely stable community structure, assisting in host physiological and immunological functions. Changes to this structure can be injurious to the health of the host, a concept termed dysbiosis. Psychological stress is a factor that has been implicated in causing dysbiosis, and studies performed by our lab have shown that restraint stress can indeed shift the cecal microbiota structure as well as increase the severity of a colonic infection caused by Citrobacter rodentium.

Gut microbiome composition is associated with temperament during early childhood.

Background: Understanding the dynamics of the gut-brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. As such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans.

Methods: We used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18-27months of age.