Gut Microorganisms And Neurological Disease Perspectives Part 2

Gut microbiota composition in modulating nervous functions

Experiments on germ-free animals have demonstrated that colonization of the gut microbiota is a key requirement for the development of the CNS and ENS and that inefficient colonization of the microbiota leads to altered gene expression and synthesis of neurotransmitters as well as altered gut sensory-motor functions [41–45]. 

The relationship between intestinal flora and memory has been a research area that has received much attention in recent years. Studies have found that the microorganisms in the intestinal flora are more closely connected to the brain, affecting our physical and mental health.

First of all, the intestinal flora has an important impact on physical health. Microorganisms in the intestine can digest food and produce nutrients to help maintain physical health. When the intestinal flora is imbalanced, it will lead to problems such as poor nutrient absorption and immune system disorders, which will in turn affect the health of the body.

However, the intestinal flora not only affects physical health but is also closely related to memory. Studies have shown that microorganisms in the intestinal flora can enter the blood circulation and brain from the intestines and affect their functions. Intestinal flora imbalance may increase the risk of Alzheimer's disease and other neurodegenerative diseases.

At the same time, the intestinal flora also affects emotions and mental state. Bacteria in the intestine release chemicals that affect the release of neurotransmitters in the brain, thereby affecting the mental state. This is why we sometimes feel uncomfortable in the stomach and become irritable.

Therefore, maintaining the health of the intestinal flora is very important for the health of our entire body. How to maintain intestinal health? The first thing is to stick to the regular diet, maintain a healthy diet structure, eat more foods rich in dietary fiber, and eat less processed foods and high-fat, high-sugar foods. The second is to focus on exercise and stress reduction, maintain a happy mentality, and a positive attitude towards life to reduce the negative impact of the intestine and psychology.

Finally, we should realize that the intestinal flora is closely related to our health. Pay attention to maintaining intestinal and psychological health, take care of your body from many aspects such as diet and exercise, and make yourself have better health. It can be seen that we need to improve memory, and Cistanche can significantly improve memory because Cistanche has antioxidant, anti-inflammatory, and anti-aging effects, which can help reduce oxidation and inflammatory reactions in the brain, thereby protecting the health of the nervous system. In addition, Cistanche can also promote the growth and repair of nerve cells, thereby enhancing the connectivity and function of the neural network. These effects can help improve memory, learning ability, and thinking speed, and can also prevent the occurrence of cognitive dysfunction and neurodegenerative diseases.

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Similarly, nutrients present in the GI tract initiate cascades of neural and hormonal events, signaling the brain about continuous nutritive changes. Afferent nerve fibers carry information from the gut to the subcortical and cortical centers of the brain, and effector fibers carry information to the smooth muscles of the gut [46]. 

Gut hormones released from the intestinal cells often transmit information to the brain by directly communicating with the CNS through the afferent fibers. Others are directly released into the circulatory system, with their effects usually being felt after they enter the brain [47]. 

Vagus nerve stimulation of the parasympathetic system of the ANS is essential for the gut microbiota to influence neurophysiological function [48]. 

An experiment with vasectomized mice showed no sign of progression in behavioral properties even after treating with the probiotic Lactobacillus rhamnosus, thus indicating that stimulation of the vagus nerve and transmission of signals via the vagus nerve is crucial in bringing about behavioral changes [49]. 

Transmission of the message from the intestine to the brainstem by the stimulated vagus nerve via the nuclei and node ganglion represents the relay input-brain-brain axis connection. Enteroendocrine cells secrete peptide hormones, which tend to activate the vagus nerve, hence conveying information to the brain [50]. 

The positioning of enteroendocrine cells close to the lumen as well as the gut microbiota facilitates interaction with the gut microbes via the metabolites produced, thus maintaining the secretion of specific peptide hormones. 

Moreover, metabolites synthesized by the microbiota are often taken in by the circulatory system, whereas metabolites with shapes similar to that of sugars and vitamins are transported actiusingns of specific transporters [51]. 

Metabolites can also pass the membrane if the epithelium is breached, allowing other microbes to escape the barrier, thus resulting in microbial imbalance or dysbiosis followed by inflammation. 

Therefore, the circulatory system controls the transmission of signals to the brain along with metabolite transportation. The gut microbiota releases molecules such as lipopolysaccharides (LPSs) and peptidoglycans, which trigger the immune response. In specific cases, LPS-synthesizing gram-negative bacteria are displaced from the gut to the circulatory system, thus activating peripheral immune reactions. 

Experiments demonstrate the development of behavioral defects such as depression as a result of peripheral immune activation [52]. 

Studies with germ-free mice display a correlation between gut microbes and the resulting immune response, thus suggesting the influence of the microbiota on neural functions via the immune response [53]. 

Additionally, the gut microbiome can interact with the brain via the expression and synthesis of neurotransmitters such as serotonin, GABA, melatonin, histamine, and acetylcholine and neurotrophic factors such as brain-derived neurotrophic factor (BDNF), which in turn influences ENS activity [54,55].

One study has suggested that the growth-associated microbiota can facilitate the development of early neurons via a process known as neurogenesis as well as oligodendrocytes and that this may be mediated by the effects of neuroinflammation and circulating IGF-1 [56]. 

Another study using adult germ-free mice models showed that the lack of normal gut microbiota is associated with increased permeability of the blood-brain barrier (BBB) [57].

Role of the brain in the modulation of gut functions

The brain plays a leading role in controlling gut functions (i.e., variations in motility, acid secretion, mucosal immune response, ensuring proper maintenance of the mucus layer and biofilm) [58]. 

The brain also tends to influence the microbiota composition as well as its function through changes in intestinal permeability. One study suggested that acute stress contributes to morphological alteration of the epithelial barrier of the colon and lower mRNA expression of the tight junction protein ZO-2 [59] and thus may allow gut microorganisms to diffuse through. The brain directs immune functions through the ANS. 

The CNS may also influence mast cell activity, and mast cell mediator release may lead to gut dysfunction. One study suggested that stress can modulate mast cell activity and lead to histamine and tryptase release [60]. 

Mast cell products such as corticotropin-releasing factor tend to increase epithelial permeability, hence facilitating bacterial access to immune cells in the lamina propria. Mild stress in adult rats as a result of neonatal maternal separation is associated with the development of colonic barrier dysfunction induced by corticotropin-releasing hormone receptors [61]. 

Laboratory experiments in mice have shown that bilateral olfactory bulbectomy results in the induction of depression, resulting in higher expression of central corticotropin-releasing hormone as well as serotonin levels [62]. 

These changes were found to be associated with an altered gut microbial profile. Norepinephrine secretion during stress leads to Pseudomonas aeruginosa virulence expression, which may cause gut sepsis [63], and thus stress may lead to the expression of virulence factors by specific gut microorganisms in the appropriate host. 

Norepinephrine also induces the proliferation of many different strains of enteric microbes and might lead to greater growth of pathogenic and nonpathogenic Escherichia coli. 

Evidence indicates that the gut microbiota plays a key role in bidirectional communication between the gut and the nervous system. Its interaction with the CNS is associated with anxiety, stress, and memory function. In addition, the CNS also tends to affect microbial composition through disturbance of the mucosal habitat. 

This is how the gut microbial community influences the human brain and, usually, the whole body, as the brain defines how a human body should function. Therefore, a significant disruption in the gut microbiota can lead to the impairment of overall body function and hence cause or contribute to the onset or progression of specific diseases or health complications. 

Again, because of the direct communication with the brain, the impacts on neurological function are more prevalent than other complications manifested as a result of impairment of the CNS by microbiome community disruption.

Association of gut microorganisms with neurological disorders

Autism spectrum disorder

Autism spectrum disorder (ASD) is a neuropsychiatric disorder that is characterized by stereotyped behaviors, cognitive inability cities, and deficits in communication or social interactions [64,65]. 

The term 'spectrum' indicates variations in the type and severity of symptoms; patients in the mild range are likely to function independently, whereas those with severe symptoms may require substantial support in their daily lives. 

The disease arises before 3 years of age, usually affects one of every 68 chi, children and is four times more prevalent in males than females [66,67]. In addition to being heterogeneous, the disorder is characterized by an obscure pathophysiology as well as etiological mechanisms related to the impaired gut microbiota, such as glutamate excitotoxicity, oxidative stress, stress, and neuroinflammation [68]. 

Physiological factors that tend to highlight the influence of the gut microbiota on autism may include autoimmune reactions, food reactions, upper GI disease, abnormal stool, autistic enterocolitis, leaky gut syndrome, excessive inflammation, aberrant glutathione levels and irregular metal or mineral levels [69]. 

In children with autism, intestinal permeability may lead to a leaky resulting the gthe in the absorption of neurotoxic molecules across a gut membrane damaged by inflammation, leading to neurological disorders [70,71]. 

Following the development of a leaky gut, which enables molecules to enter the bloodstream, immune activation, tissue damage, and brain tissue damage may emerge over time. 

Opioid peptides produced by certain diets may also influence autism-like behavioral patterns, such as decreased socialization, decreased response to pain, abnormal language, and self-abusive or repetitive behaviors through interference with the function of neurotransmitters. 

However, a direct link has yet to be identified. Studies have further observed that children with ASD prefer starches, snacks, and processed food while rejecting fruits, vegetables, and proteins [72,73]. 

Although an imbalance in the gut microbiota may lead to gut dysbiosis, several pathogenic bacteria may lead to neurological disorders, in the presence of a weakened immune system. 

Toxins produced by the bacteria may build up in the bloodstream, leading to confusion, delirium, and even coma. Yeasts are also known to contribute to neurological diseases since they are known to produce the contributing chemicals and have also been found in increased levels in ASD patients [74]. 

The linking etiology between the gut microbiota and autism was confirmed after the transplantation of gut microbiota from autistic donors into germ-free mice led to the induction of autistic behaviors in a rodent model [75]. 

A hypothesis by Williams et al. suggests that children with ASD lack Bacteroidetes, which are important drivers of polysaccharide digestion, and therefore ASD patients not only have anomalous carbohydrate breakdown ability but also have mucosal dysbiosis [76]. 

Following this, a metagenomic analysis showed that ASD patients had decreased Bacteroidetes, an increase in the ratio of Firmicutes to Bacteroidetes, and an increase in Betaproteobacteria [77]. 

Moreover, a pyrosequencing study of fecal microflora revealed major differences in the Actinobacteria and Proteobacterium phyla in comparison with healthy controls [76]. This pyrosequencing study along with three other studies, also revealed an increased number of Desulfovibrio species and Bacteroides vulgatus in stools of ASD patients [78–80]. 

Desulfovibrio species are also associated with increased propionic acid production, which could contribute to ASD pathogenesis [81]. In addition, lower levels of Akkermansia, bacteria that degrade mucin in children with ASD, indicated a thinner GI mucosal barrier compared with controls. This may lead to impaired gut permeability in children with ASD [82,83]. 

Another study showed that the number and type of Clostridium and Ruminococcus species differed significantly in normal children compared with ASD children when cultivated using basic anaerobic culturing techniques to count and isolate microorganisms followed by PCR targeting of 16S rDNA in the isolates [78]. 

Following this, a study by Song et al. demonstrated that Clostridium cluster groups I and XI and Clostridium bolteae were significantly higher in children with autism when quantitative real-time PCR was used [84].

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