Adolescence, the Microbiota-Gut-Brain Axis, and the Emergence of Psychiatric Disorders.

Second only to early life, adolescence is a period of dramatic change and growth. For the developing young adult, this occurs against a backdrop of distinct environmental challenges and stressors. A significant body of work has identified an important role for the microbiota-gut-brain (MGB) axis in the development and function of the brain.

Animal models of visceral pain and the role of the microbiome.

Visceral pain refers to pain arising from the internal organs and is distinctly different from the expression and mechanisms of somatic pain. Diseases and disorders with increased visceral pain are associated with significantly reduced quality of life and incur large financial costs due to medical visits and lost work productivity. In spite of the notable burden of illness associated with those disorders involving increased visceral pain, and some knowledge regarding etiology, few successful therapeutics have emerged, and thus increased attention to animal models of visceral hypersensitivity is warranted in order to elucidate new treatment opportunities.

The Effect of Microbiota on Behaviour.

There is currently enormous interest in the impact of the intestinal microbiota on the development and function of the brain via activity of the microbiota-gut-brain axis. It has long been recognised that symbiotic microorganisms influence host behaviour, but in recent years evidence has accumulated that this can, in fact, be beneficial to the host. Indeed, substantial research has now demonstrated an influence of the intestinal microbiota on a wide range of mammalian behaviours.

Publisher Correction: Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment.

There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning.

Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling.

The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI).

Disruptive physiology: olfaction and the microbiome-gut-brain axis.

This review covers the field of olfaction and chemosensation of odorants and puts this information into the context of interactions between microbes and behaviour; the microbiome-gut-brain axis (MGBA). Recent emphasis has also been placed on the concept of the holobiome which states that no single aspect of an organism should be viewed separately and thus must include examination of their associated microbial populations and their influence. While it is known that the microbiome may be involved in the modulation of animal behaviour, there has been little systematized effort to incorporate into such studies the rapidly developing knowledge of the wide range of olfactory systems.

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior.

There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice.

Posttraumatic Stress Disorder: Does the Gut Microbiome Hold the Key?

Gut bacteria strongly influence our metabolic, endocrine, immune, and both peripheral and central nervous systems. Microbiota do this directly and indirectly through their components, shed and secreted, ranging from fermented and digested dietary and host products to functionally active neurotransmitters including serotonin, dopamine, and γ-aminobutyric acid. Depression has been associated with enhanced levels of proinflammatory biomarkers and abnormal responses to stress.

Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate.

The gut microbiome has been shown to regulate the development and functions of the enteric and central nervous systems. Its involvement in the regulation of behavior has attracted particular attention because of its potential translational importance in clinical disorders, however little is known about the pathways involved. We previously have demonstrated that administration of Lactobacillus rhamnosus (JB-1) to healthy male BALB/c mice, promotes consistent changes in GABA-A and -B receptor sub-types in specific brain regions, accompanied by reductions in anxiety and depression-related behaviors.

Microbiota and the gut-brain axis.

Changes in gut microbiota can modulate the peripheral and central nervous systems, resulting in altered brain functioning, and suggesting the existence of a microbiota gut-brain axis. Diet can also change the profile of gut microbiota and, thereby, behavior. Effects of bacteria on the nervous system cannot be disassociated from effects on the immune system since the two are in constant bidirectional communication.

Microbes taming mast cells: Implications for allergic inflammation and beyond.

There is increasing awareness of a relationship between our microbiota and the pathogenesis of allergy and other inflammatory diseases. In investigating the mechanisms underlying microbiota modulation of allergy the focus has been on the induction phase; alterations in the phenotype and function of antigen presenting cells, induction of regulatory T cells and shifts in Th1/Th2 balance. However there is evidence that microbes can influence the effector phase of disease, specifically that certain potentially beneficial bacteria can attenuate mast cell activation and degranulation.

The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin.

Background: The microbiome is essential for normal myenteric intrinsic primary afferent neuron (IPAN) excitability. These neurons control gut motility and modulate gut-brain signaling by exciting extrinsic afferent fibers innervating the enteric nervous system via an IPAN to extrinsic fiber sensory synapse. We investigated effects of germ-free (GF) status and conventionalization on extrinsic sensory fiber discharge in the mesenteric nerve bundle and IPAN electrophysiology, and compared these findings with those from specific pathogen-free (SPF) mice.

Gut commensal microvesicles reproduce parent bacterial signals to host immune and enteric nervous systems.

Ingestion of a commensal bacteria, Lactobacillus rhamnosus JB-1, has potent immunoregulatory effects, and changes nerve-dependent colon migrating motor complexes (MMCs), enteric nerve function, and behavior. How these alterations occur is unknown. JB-1 microvesicles (MVs) are enriched for heat shock protein components such as chaperonin 60 heat-shock protein isolated from Escherichia coli (GroEL) and reproduce regulatory and neuronal effects in vitro and in vivo.

Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions.

Human milk oligosaccharides (HMO) are being studied by different groups exploring a broad range of potential beneficial effects to the breastfed infant. Many of these effects have been attributed to a growth promotion effect on certain gut organisms such as bifidobacteria. Additionally, evidence indicates that HMO are able to directly promote positive changes in gut epithelium and immune responses under certain conditions.

The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse.

Background: The role of intestinal microbiota in the development and function of host physiology is of high interest, especially with respect to the nervous system. While strong evidence has accrued that intestinal bacteria alter host nervous system function, mechanisms by which this occurs have remained elusive. For this reason, we have carried out experiments examining the electrophysiological properties of neurons in the myenteric plexus of the enteric nervous system (ENS) in germ-free (GF) mice compared with specific pathogen-free (SPF) control mice and adult germ-free mice that have been conventionalized (CONV-GF) with intestinal bacteria.