Bacteria and Brains, the relationship between the gut microbiome and neuron

The human microbiome is all over the news , and what we choose to eat to ensure an optimal flora is a big topic of discussion.  The discovery of the size and complexity of the human microbiome.

The once-wild idea that intestinal bacteria influence mental health has transformed into a major research pursuit. There is lots of interest in the ‘gut-brain’ axis.

By now, the idea that gut bacteria affect a person’s health is not revolutionary. Many people know that these microbes influence digestion, allergies, and metabolism. The trend has become almost commonplace: New books appear regularly detailing precisely which diet will lead to optimum bacterial health.

 

It is now clear that there is bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms.

What we know

1. Psychological and physical stresses affect the composition and the metabolic activity of the gut microbiota.

2. experimentally induced changes to the gut microbiome can affect brain systems responsible for  emotional behavior.

These two findings have resulted in speculation that alterations in the gut microbiome may play a role, maybe an critical role,  in human conditions including autism spectrum disorder, anxiety, depression, and chronic pain.

What are the mechanisms by which microorganisms shape aspects of brain functioning such as memory and social behaviour, and how they might contribute to conditions such as depression and neurodegenerative disease, are tenuous and often controversial.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228144/

Gut Microbes and the Brain: Paradigm Shift

People are looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli using large-scale population-based studies of the gut microbiome and brain imaging seeking to validate these speculations.

What do we know

 

Psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota.

experimental changes to the gut microbiome can affect emotional behavior and related brain systems.

These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain.

The often quoted and remarkable ability of the parasite Toxoplasmosis gondii of hijacking the host’s (e.g., rat) brain systems related to defensive behaviors and sexual attraction to manipulate the rat’s behavior in a way that optimizes reproduction of the parasite () was considered an interesting outlier in the prevalent dogma of looking exclusively at the brain for causes of behavior and brain diseases.

One exception to the traditional view has been autism spectrum disorder (ASD), a brain disease that has long been suspected to be related to altered gut microbiota (), a concept that has recently been revisited both in rodent models and in human subjects.

The “microbiome-free” worldview of neuroscience has dramatically changed with the discovery and characterization of the human microbiome and, in particular, with the gut microbiome ().

Although gut-brain interactions have been studied for decades, providing a wealth of information about the close interactions between the gut-associated immune system, enteric nervous system, and gut-based endocrine system (), these findings have largely been ignored by the psychiatric and neurological research community.

The discovery of the gut microbiome has added a long overlooked component to the complex bidirectional signaling between mind, brain, gut, and its microbiome.

The initial skepticism about reports suggesting a profound role of an intact gut microbiota in shaping brain neurochemistry and emotional behavior has given way to an unprecedented paradigm shift in the conceptualization of many psychiatric and neurological diseases.

Although many of the new concepts are primarily based on the intriguing experimental findings in rodents, initial studies in humans seem to support the notion that there is a relationship between the complex world of microbiota in our intestines and brain structure and function.

Even though the majority of published studies of gut microbiome to brain signaling are based on microbiome analyses from stool samples, future studies will almost certainly expand the scope of investigations to mucosal samples taken from different regions of the gastrointestinal tract.

Based on our current, still limited knowledge about these gut-microbiome-brain interactions, intriguing speculations have been proposed in a rapidly increasing number of review articles on the topic.

They range from terms, such as “psychobiotic” or “melancholic” microbes (), to concepts that humans are just the vehicle for the 100 trillion microorganisms living inside of us. The latter concept has been developed into the intriguing hypothesis that the gut microbiota have developed ways to “hack” into our reward system to make us crave certain foods and avoid others that are most beneficial to them ()..

Similarly, microbe-brain interactions have been recently proposed to be a key driver of the evolution of the social brain ().

The following review addresses some aspects of the rapidly evolving topic of gut-microbiome-brain interactions in health and disease (Fig. 1).

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Bidirectional communication channels between the gut microbiome, the gut, and the brain. Endocrine-, neurocrine-, and inflammation-related signals generated by the gut microbiota and specialized cells within the gut can, in principal, affect the brain. In turn, the brain can influence mi crobial composition and function via endocrine and neural mechanisms.

Gut microbiota regulates stress, anxiety, and cognition: mechanisms and therapeutic potential

Accumulating evidence from animal studies, suggests that different types of psychological stress can affect the composition of the gut microbiota.

For example, maternal separation, restraint conditions, crowding, heat stress, and acoustic stress all alter the composition of the gut microbiota ().

In addition, a growing body of data suggests that the microbiota may be involved in controlling behaviors relevant to stress-related disorders.

Several experimental conditions have been used to study the role of the gut microbiota in preclinical models, including perturbation of the gut microbiome by ingestion of probiotics and antibiotics, fecal microbial transplant, and comparison of behaviors and biological readouts between germ-free animals (raised in a sterile environment from the time of birth) and those with a pathogen-free microbiome.

 since ) discovered that germ-free mice have an exaggerated hypothalamic-pituitary-adrenal axis response to restraint stress, an effect that was reversed by monocolonization with a particular Bifidobacterium species.

This seminal observation motivated a number of research groups to investigate the role of the host gut microbiota on CNS function, with converging and intriguing results.

Despite exaggerated neuroendocrine responses to stress, consistent reductions in anxiety-like behavior were observed in germ-free mice exposed to more ecologically relevant stressors, such as novel and aversive environments (elevated plus maze, light/dark box, open field) ().

This phenotype was susceptible to reversal when animals were colonized early in life ().

Interestingly, recent studies in germ-free animals in the stress-sensitive F344 rat strain showed similar exaggerated neuroendocrine responses but also revealed an increase in anxiety-like behavior ().

Moreover, it has recently been shown that short-term colonization of germ-free mice in adulthood reduced anxiety-like behaviors ().

Together, it is clear that studies in germ-free animals clearly show a relationship between gut microbiota and stress and anxiety-related behaviors, the nature of this relationship being influenced by temporal, sex, strain, and species factors that are not yet fully understood.

A growing number of studies are also investigating gene expression changes in different brain regions in germ-free mice. Most commonly, decreases in the hippocampal expression of BDNF, a key protein involved in neuronal plasticity and cognition, have been observed in germ-free mice relative to conventionally raised or conventionalized (i.e., initially germ-free mice colonized with the normal mouse gut microbiota) controls.

Similar changes in BDNF expression have also been reported following antibiotic administration ().

Alterations in neurotransmitter signaling, including neurotransmitters and associated metabolites and neurotransmitter receptors, have also been described in specific brain regions of germ-free mice.

) took a genome-wide transcriptomic approach showing that genes associated with the citrate cycle (synaptic long-term potentiation, steroid hormone metabolism, and cyclic adenosine 5-phosphate-mediated signaling) were upregulated in germ-free mice. Interestingly, in these studies, the cerebellum and hippocampus have robust changes in gene expression, but the hypothalamus, the brain region involved in the stress response, showed almost no differential gene expression.

Some behavioral and biochemical parameters (including anxiety, sociability, hypothalamic-pituitary-adrenal axis, and tryptophan metabolism) could be reversed in germ-free mice by recolonization with a conventional microbiota or probiotic treatment, but others were unaffected by restoration of a normal microbiota (including 5-HT concentration and social cognition) ().

 

start with probiotics here…..

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https://www.nature.com/articles/d41586-019-00483-5

Links between gut microbes and depression strengthened

 

Much of what we know so far is based on studies showing correlations between specific gut bacteria, their metabolites and neurological symptoms. But these correlations do not prove cause and effect. Many studies use animal models, which don’t accurately mirror human traits or behaviours. Human studies have been limited: they’re usually based on relatively small numbers of people, and might not control for a wealth of confounding factors — such as unusual diets, antibiotics or antidepressants — that can affect the microbiota.