Comparison of Glucose Metabolizing Properties of Enterobacterial Probiotic Strains In Vitro.

Before the absorption in the intestine, glucose encounters gut bacteria, which may serve as a barrier against hyperglycemia by metabolizing glucose. In the present study, we compared the capacity of enterobacterial strains to lower glucose levels in an in vitro model of nutrient-induced bacterial growth. Two probiotic strains, () and () , as well as , were studied.

Long-Term Dynamics of Serum α-MSH and α-MSH-Binding Immunoglobulins with a Link to Gut Microbiota Composition in Patients with Anorexia Nervosa.

Introduction: Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition.

Methods: The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit and 41 healthy controls, all females.

Functional role of immunoglobulin G as an oxytocin-carrier protein.

It has been long-time known that oxytocin in plasma is bound to a carrier protein, a common feature of circulating peptide hormones, however, the nature of such protein was uncertain. A recent study revealed that about 60% of oxytocin present in plasma is bound to immunoglobulin G (IgG) and that oxytocin-binding IgG plays a role of a functional oxytocin carrier protein. Here, we review the historical background and methodology leading to this discovery.

Immunoglobulin G is a natural oxytocin carrier which modulates oxytocin receptor signaling: relevance to aggressive behavior in humans.

Oxytocin is a neuropeptide produced mainly in the hypothalamus and secreted in the CNS and blood. In the brain, it plays a major role in promoting social interactions. Here we show that in human plasma about 60% of oxytocin is naturally bound to IgG which modulates oxytocin receptor signaling.

Protein Extract of a Probiotic Strain of and Bacterial ClpB Protein Improve Glucose Tolerance in Mice.

A commercial strain of () 4597 bacteria was shown to reduce food intake and promote weight loss, effects possibly induced by the bacterial protein ClpB, an antigen-mimetic of the anorexigenic α-melanocyte-stimulating hormone. A decrease in the basal plasma glucose levels was also observed in overweight fasted humans and mice receiving . However, it is not known whether influences sweet taste preference and whether its protein extract or ClpB are sufficient to increase glucose tolerance; these are the objectives tested in the present study.

Lactobacillus salivarius and Lactobacillus gasseri supplementation reduces stress-induced sugar craving in mice.

Objective: Increased intake of sweets or sugar craving may occur in response to chronic stress representing a risk factor for development of eating disorders and obesity. However, no safe treatment of stress-induced sugar craving is available. In this study we analysed effects of two Lactobacillus strains on food and sucrose intake in mice before and during their exposure to a chronic mild stress (CMS).

Gut Microbiota-Brain Axis in Regulation of Feeding Behavior.

The survival of microorganisms inhabiting the intestinal tract depends on the nutrients provided by the host, with the latter obtaining them through food intake. It is hence not surprising that the co-evolution of gut bacteria and their hosts, including humans, shaped intrinsic interactions between their respective metabolisms with an impact on host feeding behavior. Understanding molecular pathways underlying such interactions may aid in the development of new therapeutic approaches for several pathological conditions accompanied by altered feeding behavior.

Blood Levels of Neuropeptide 26RFa in Relation to Anxiety and Aggressive Behavior in Humans-An Exploratory Study.

26RFa, also referred to as QRFP, is a hypothalamic neuropeptide mainly known for its role in the regulation of appetite and glucose metabolism. Its possible relevance to emotional regulation is largely unexplored. To address this, in the present exploratory study, we analyzed the plasma concentrations of 26RFa in humans characterized by different levels of anxiety and aggressive behavior.

Neurotensin-Binding Immunoglobulin G in Patients with Parkinson's Disease.

Introduction: Neurotensin (NTS) is a 13-amino acid neuropeptide functionally linked with the brain dopaminergic system via expression of the NTS peptide or its receptor in dopamine neurons. Neuropeptide-binding immunoglobulins (Igs) are present in humans and can be involved in both physiological and pathological processes. Considering the functional link between NTS and dopamine neurons, we studied the occurrence of NTS-binding IgG autoantibodies in patients with Parkinson's disease (PD).

The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

Background: Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation.

The effects of probiotics administration on the gut microbiome in adolescents with anorexia nervosa-A study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

Objective: Knowledge on gut-brain interaction might help to develop new therapies for patients with anorexia nervosa (AN), as severe starvation-induced changes of the microbiome (MI) do not normalise with weight gain. We examine the effects of probiotics supplementation on the gut MI in patients with AN.

Method: This is a study protocol for a two-centre double-blind randomized-controlled trial comparing the clinical efficacy of multistrain probiotic administration in addition to treatment-as-usual compared to placebo in 60 patients with AN (13-19 years).

Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation.

The worldwide prevalence of metabolic diseases such as obesity, metabolic syndrome and type 2 diabetes shows an upward trend in recent decades. A characteristic feature of these diseases is hyperglycemia which can be associated with hyperphagia. Absorption of glucose in the small intestine physiologically contributes to the regulation of blood glucose levels, and hence, appears as a putative target for treatment of hyperglycemia.

The Probiotic Strain HA4597 Improves Weight Loss in Overweight Subjects under Moderate Hypocaloric Diet: A Proof-of-Concept, Multicenter Randomized, Double-Blind Placebo-Controlled Study.

: Increasing evidence supports the role of the gut microbiota in the control of body weight and feeding behavior. Moreover, recent studies have reported that the probiotic strain HA4597 (HA), which produces the satietogenic peptide ClpB mimicking the effect of alpha-MSH, reduced weight gain and adiposity in rodent models of obesity. : To investigate the clinical efficacy of HA, 236 overweight subjects were included, after written informed consent, in a 12-week prospective, double-blind, randomized study.

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach.

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon.

Plasma enterobacterial ClpB levels and ClpB- and α-MSH-reactive immunoglobulins in lung cancer patients with and without anorexia.

Objectives: Anorexia represents a common and debilitating clinical problem in patients with several forms of cancer, in particular lung cancer, but its mechanisms are not completely understood. Recently, the caseinolytic-protease-B (ClpB) homologue protein, produced by common gut bacteria, such as Escherichia coli, was identified as an antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. ClpB was previously detected in human plasma and displayed satietogenic properties; however, its possible relevance to cancer anorexia has not yet been investigated.

Host Starvation and Female Sex Influence Enterobacterial ClpB Production: A Possible Link to the Etiology of Eating Disorders.

Altered signaling between gut bacteria and their host has recently been implicated in the pathophysiology of eating disorders, whereas the enterobacterial caseinolytic protease B (ClpB) may play a key role as an antigen mimetic of α-melanocyte-stimulating hormone, an anorexigenic neuropeptide. Here, we studied whether ClpB production by gut bacteria can be modified by chronic food restriction and female sex, two major risk factors for the development of eating disorders. We found that food restriction increased ClpB DNA in feces and ClpB protein in plasma in both male and female rats, whereas females displayed elevated basal ClpB protein levels in the lower gut and plasma as well as increased ClpB-reactive immunoglobulins (Ig)M and IgG.

Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice-a new potential probiotic for appetite and body weight management.

Background/objectives: Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity.

Methods: The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.

Food intake and meal pattern in response to hyperosmotic-induced dehydration in obese and lean Zucker rats.

Objectives: Obese Zucker rats display neurochemical modifications in the brain characteristic of dehydration, but are nevertheless hyperphagic. This suggests that the obese animals can be resistant to dehydration-induced anorexia. The aim of this study was to test the hypothesis by comparing the effects of dehydration on food intake and feeding pattern between obese and lean Zucker rats.

HA4597 Strain Reduces Food Intake and Body Weight Gain and Improves Body Composition, Glucose, and Lipid Metabolism in a Mouse Model of Hyperphagic Obesity.

Use of new generation probiotics may become an integral part of the prevention and treatment strategies of obesity. The aim of the present study was to test the efficacy of a potential probiotic strain of lactic bacteria ( ) HA4597™, in a mouse model of obesity characterized by both hyperphagia and diet-induced adiposity. For this purpose, 10-week-old high-fat-diet (HFD)-fed hyperphagic / male mice received a daily treatment with 1.

Neurobiology of Aggressive Behavior-Role of Autoantibodies Reactive With Stress-Related Peptide Hormones.

Adrenocorticotropic hormone together with arginine vasopressin and oxytocin, the neuropeptides regulating the stress response and the hypothalamic-pituitary-adrenal axis activity, are known to modulate aggressive behavior. The functional role of the adrenocorticotropic hormone immunoglobulin G autoantibodies in peptidergic signaling and motivated behavior, including aggression, has been shown in experimental and models. This review summarizes some experimental data implicating autoantibodies reactive with stress-related peptides in aggressive behavior.

Proteome modifications of gut microbiota in mice with activity-based anorexia and starvation: Role in ATP production.

Objective: Activity-based anorexia (ABA) in rodents is a behavioral model of anorexia nervosa, characterized by negative energy balance, hyperactivity, and dysbiosis of gut microbiota. Gut bacteria are known to produce energy substrates including adenosine triphosphate (ATP) and acetate. The aim of this study was to determine whether ABA alters the proteome of gut microbiota relevant to ATP and acetate production.

Effects of Macronutrients on the In Vitro Production of ClpB, a Bacterial Mimetic Protein of α-MSH and Its Possible Role in Satiety Signaling.

Gut microbiota can influence the feeding behavior of the host, but the underlying mechanisms are unknown. Recently, caseinolytic protease B (ClpB), a disaggregation chaperon protein of , was identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. Importantly, ClpB was necessary for to have an anorexigenic effect in mice, suggesting that it may participate in satiety signaling.

On the origin of eating disorders: altered signaling between gut microbiota, adaptive immunity and the brain melanocortin system regulating feeding behavior.

Research in the field of gut microbiota - brain axis may contribute to clarifying the origin of anorexia nervosa and bulimia, the two principal forms of eating disorders (ED). The initial key findings in ED patients of plasma immunoglobulins (Ig) that react with α-melanocyte-stimulating hormone (α-MSH), a neuropeptide in the brain signaling satiety, have initiated further studies leading to the discovery of the origin of such autoantibodies and to the understanding their possible functional role. An anorexigenic bacterial protein Escherichia coli caseinolytic protease B was recently found to be responsible for the production of α-MSH-cross-reactive autoantibodies and this protein was also detected in human plasma.

Immunoglobulin G modulation of the melanocortin 4 receptor signaling in obesity and eating disorders.

Melanocortin 4 receptor (MC4R) plays a key role in regulation of appetite activated by its main ligand α-melanocyte-stimulating hormone (α-MSH) in both central and peripheral targets. α-MSH also binds to circulating immunoglobulins (Igs) but the functional significance of such immune complexes (ICs) in MC4R signaling in normal and pathological conditions of altered appetite has remained unknown. To address this question, we analyzed plasma levels, affinity kinetics, and binding epitopes of α-MSH-reactive IgG extracted from plasma samples of female patients with hyperphagic obesity, anorexia nervosa, bulimia nervosa, binge-eating disorder, and healthy controls.