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Research

Probiotics

While germ-free (GF) mice and fecal examination are two ways of examining the microbiome, an effective approach of studying the impact of the microbiome in humans is the utilization of probiotics due to an element of control. . Probiotics are a combination of various live bacteria and yeasts that are introduced into the digestive system in a powder capsule, or added to food products. A systematic review from 2016 examined the preclinical and small human trials that have been conducted with certain commercially available strains of probiotic bacteria and found that among those tested, Bifidobacterium and Lactobacillus genera (B. longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei), had the most potential to be useful for certain central nervous system disorders.

Researchers can use certain types of probiotics to target specific bacteria and, as a result, the brain networks, behaviors, or cognitive domains affected by those bacteria. Additionally, researchers can control the amount of probiotics used, as well the amount of time participants have to take the treatments. This helps researchers to examine both the behavior of participants who undergo a series of treatments, as well as their neuronal functioning through fMRI, EEG, and neuropsychological test performance.

Autism

Studies using GF mice indicate a relationship between autism and microbiome. Three-chamber sociability tests are used to observe autistic behavior in mice, and in these tests mice are placed in a middle chamber and they can make the decision to go to either a chamber with other mice or a chamber with no mice. Typically, a mouse would prefer to go to the chamber containing other mice. However, this is not the case with GF mice. Thus, a lack of a diverse microbiome leads to autistic behavior. Genetic analysis of GF mice via RNA extraction also shows an upregulation of synaptic plasticity-related genes such as Bdnf IV and genes that promote transcription (cFOS, Arc) in the amygdala. This leads to an over-activation of amygdala activity that mimics amygdala activity in patients with autism.

Pain

The composition of the gut microbiome can contribute to decreased pain threshold, known as visceral hypersensitivity, in functional gastrointestinal disorders through the sensitization of nociceptors. The specific pathway involved starts with nociceptive afferent fibers projecting onto spinal nociceptive neurons in the superficial laminae. Then the cingulate cortex, medial thalamus, amygdala, hypothalamus, periaqueductal gray, and solitary tract generate the perception of pain and modulate the response.

Specifically, a bacterial composition of Lactobacillus rhamnosus, L. farciminis, Bifidobacterium infantis, and B. longum have been shown to impact pain. The microbiome can lead to visceral hypersensitivity through activation of receptors involved in peripheral sensitization such as cannabinoid receptors and serotonin receptors via immune response at the mucosal level. It can also stimulate the release of pain-suppressing molecules. These natural biomolecules include opiods from neutrophils and monocytes, endocannabinoids, and monoamines.

Visceral sensitivity can also be affected by stress-modulate microbiome activity. Stress can lead to decreased gut motility and colonic inertia, which in turn negatively affects the amount and diversity of gut bacteria. Due to the fact that early postnatal life is the critical point to HPA axis development, programming of the neuroendocrine stress response, and establishment of the essential gut microbiota, maternal separation models are used to study the relationship between stress and early life on the microbiota. As a result, these studies suggest that stress in early life leads to increased vulnerability to visceral sensitivity. Furthermore, studies on stress in later life using antibiotic studies and GF mice show that animals with a lack of gut bacteria have both an exaggerated stress response and reduced perception of pain.