Journal of Multiple Sclerosis

A Review of Olfactory Dysfunction and Neurological Disorders

Maria Richards^{1* *}Correspondence: Maria Richards, Department of Neurology, University of Buffalo, United States, Email:

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Introduction

Numerous unicellular and multicellular microbial populations, including bacteria, viruses, fungi, and parasites, are hosts for all people and other animals [1]. Both in the environment and the human body, microbes are pervasive. As the host or the environment changes, they can alter or adapt. The host's health and disorders may be impacted by the microorganisms and their metabolites. Every surface of the human body, including the oropharynx, nasopharynx, respiratory system, digestive tract, urinary system, genital organs, and skin, is susceptible to the presence of bacteria. Microbial dysbiosis is a shift in the composition of the healthy microbiota that results in pathological diseases and health problems. The microbiota can be both transient and permanent; their diversity is influenced by several variables, including drugs, nearby environmental microorganisms, habitat, nutritional accessibility, and host factors, such as host hygiene, immunity, and genetics, as well as physical variables, such as oxygen, pH, moisture, and other microbial interactions. Respiratory infections start to appear as a result of opportunistic pathogen colonization, and innate immune mediators shift. The human respiratory system begins at the nostril opening (nose or anterior nares). They lead posteriorly to the lung alveoli and the nasopharynx. Airflow through the Upper Respiratory Tract (URT) is continuous. It has the highest concentration of microbial communities, which inhibits pathogen localization and spread on the mucosal surface of the Lower Respiratory Tract (LRT). The nasal microbiota differs from the URT's microbial community and does not change as an adult. Adults of middle age may start seeing changes in their nasal microbiome. Between the ages of 40 and 65, Staphylococcus, Streptococcus, Veillonella, Cutibacterium, and Corynebacterium species entirely dominate the nasal microbiota of healthy individuals. As people age, the makeup of their nasal and oropharyngeal microbiota changes and resembles that of the oropharyngeal region's microbial community. Roghmann et al. looked at the variety of nasal microbiota in elderly subjects living in independent and nursing facilities. According to the study, elderly people had an excess of Streptococcus and a relative abundance of other species in their nasal passages, including Lactobacillus reuteri, Staphylococcus epidermidis, and Rothia mucilaginosa [2]. Corynebacterium, Moraxella, Staphylococcus, Dolosigranulum, Streptococcus, Haemophilus, Peptoniphilus, Cutibacterium, Anaerococcus, Enterobacteriaceae, Pseudomonas, and Neisseria are among the respiratory tract infections (RTI)-causing bacteria found in the nasal passages of older adults (>65 years) with RTI. The following bacteria were discovered in the oropharynx: Prevotella, Veillonella, Streptococcus, Neisseria, Fusobacterium, Leptotrichia, Haemophilus, Rothia, Porphyromonas, Actinobacillus, Lactobacillus, and Staphylococcus. Moraxella catarrhalis and M. nonliquefaciens were less common among the elderly with Lower Respiratory Tract Infections (LRTI) compared to the healthy older persons, which suggests a link between Moraxella spp. and the elderly's respiratory health. M. catarrhalis and M. nonliquefaciens, on the other hand, have been linked to RTIs in young children. According to some data, a small number of microorganisms play a significant role in connecting the nasal cavity and the Central Nervous System (CNS). In the brains of AD patients, Chlamydia pneumonia, an obligate intracellular infection that causes sinusitis and pneumonia, was discovered. The oral, nasopharyngeal, and cutaneous niches of Propionibacterium acnes were found in higher concentrations in the post-mortem investigations of AD brains. Corynebacterium diphtheria's diphtheria toxin can reach the central nervous system and cause sporadic AD. Parkinson's disease has been linked to some changes in the mucosal sensory nerve terminals of the oropharynx, larynx, upper esophagus, and gut, in addition to neuropathological changes (PD). The gut microbiota connects the gut and brain by causing bidirectional communication through the integration of the gut-brain immunological mediators, much as how the nasal microbiota is involved in neurodegenerative disorders. Because Lewy bodies, also known as -synuclein, accumulate in the central nervous system, PD is primarily defined by the death of dopaminergic neurons in the substantia nigra [3]. The loss of neurons and synaptic components is caused by the development of amyloid- (A; a short peptide found in the amyloid plaques of the AD brain) plaques and neurofibrillary tangles of the phosphorylated tau proteins in the case of AD. The mucosal barrier, gut, lungs, and microbiota are all profoundly impacted by the macro- and micronutrients of the diet [4]. A balanced diet may contribute to the prevention of mental illnesses by enhancing the gut-brain axis. Neurodevelopmental problems have been linked to diet and lifestyle. Short-chain Fatty Acids (SCFAs), including acetate, propionate, and butyrate, are produced as a result of the utilization of dietary fibers by the Firmicutes, Bacteroidetes, Bifidobacterium, and Prevotella members of the gut microbiota (Firmicutes, Bacteroidetes, and Bifidobacterium). These SCFAs are essential for gut epithelial and immune The pathogen entrance point and the host's response have an impact on the course of the disease. The URT and nasal barrier are crucial in infection prevention. Although the human nasal mucosa supports a variety of microbial communities, the URT served as the primary entry point for the coronavirus illness 2019 (COVID-19). The nasal or respiratory tract microbiota may have a role in the etiology of COVID-19. However, further research is required to fully understand how the SARS-CoV-2 infection affects the microbiota in the upper airways. The current study outlines the interactions between the development of NDs with age, respiratory tract infections, olfactory dysfunctions, and nasal microbiota dysbiosis. The study also discusses how nutrition, microbiome, and the brain are interconnected, as well as how COVID-2019 contributed to the NDs. Olfactory dysfunction and neurological disorders.

People who have olfactory impairments struggle in many aspects of daily life. One of the essential senses connected to human health and well-being is odour. Dysfunctional olfaction is a sign of major illnesses. The olfactory identification process takes a different path, for example, when the odour material binds to the olfactory receptors. This chemical binding causes electrochemical signals to be released inside the olfactory neurons, which are then transmitted to the olfactory regions of the brain, where they are then stimulated, ultimately leading to an emotional response. Olfactory impairment is significantly influenced by age. Adults in their middle years and beyond suffer the greatest loss of olfactory function. The possibility of aging-related olfactory impairment was researched by Schubert et al. Their findings showed that among those aged 53–59, 70–79, and 80–97, the risk of olfactory impairment was 4.1%, 21%, and 47.1%, respectively. The findings demonstrated that olfactory function declines with age. The main ND indication is olfactory dysfunction. According to a study on changes in olfaction with aging and in some neurological illnesses, olfaction is a sophisticated sensory system that has been linked to both mood and cognition. Strong olfactory and emotional memories may result from the neurophysiological characteristics of the olfactory system and the odorant [5]. The commensal organisms that live in the nasal cavity play a role in the development of the olfactory epithelium in addition to other External Influences (OE). Analysis of the nasal microbiome's olfactory functions demonstrated that olfactory identification was unrelated to the nasal microbiota. On the other hand, the nasal microbial community is linked to the olfactory threshold and olfactory discrimination. The olfactory system and nasal microbiota of healthy participants were investigated. The volunteers were divided into groups according to their olfactory abilities, including hyposmia, normal olfactory function, and a good sense of smell. Surprisingly, the findings showed that each group's nasal cavity had a different microbial ecology. The findings demonstrated that the nasal microbiota contributes to olfactory functioning. The olfactory epithelium is modulated by the microorganisms, which has an impact on olfactory function. The phyla Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes predominate in the olfactory area's microbiome. Particularly, Corynebacterium, Staphylococcus, and Dolosigranulum species are widespread. Olfactory infections take place when the Dolosigranulum program commensal resident disrupts the normal nasal microbiota and takes over. The olfactory system allows metabolites and nasal bacteria to reach the brain. By passing the BBB, the olfactory nerve from the nasal cavity penetrates the CNS, allowing access to the Olfactory Bulb (OB) and its products through the olfactory neuro epithelium. Endothelial cells, astrocytes, neurons, and peripheral immune cells make up the BBB, which serves as an interface for the exchange of blood and chemicals in the brain. At the inter-endothelial cleft, complex tight junctions control the flow of ions and macromolecules from systemic circulation. Transcellular paracellular permeability is the pathway taken by microbial infections to enter the Central Nervous System (CNS) [6]. The olfactory receptor cells are contacted when germs from aerosols or air enter the nasal cavity through the nostrils (Orc). The neurotransmitter system and the olfactory cortices link to the tuft of olfactory nerve fibers (OC). The complex network of olfactory communication includes the reticular formation system (RFS), which is responsible for the visceral reactions to scent as well as the OC, Hippocampus (HC), Amygdala (AG), Entorhinal Cortex (EC), Hypothalamus (HT), and locus coeruleus. The ability to recognize, distinguish, and associate odors with emotions is thus made possible by the extension of the olfactory nerve fibers' connections throughout the brain. The extracellular fluid of the brain and the Central Nervous System (CNS) are both affected by the inflammatory cytokines and other immune regulators of the nasopharynx, which can affect olfactory function. Olfactory dysfunction is prevalent as people age and the OE and OB change as a result of structural changes to the nostrils. Other factors, including chronic infections, aging-related nasal epithelium atrophy, reduced mucosal blood flow, sympathetic and parasympathetic imbalance, nasal engorgement, abnormalities in the Olfactory Cortex (OC), sensory loss in the receptor cells, decreased mucosal enzymes, and changes in the neurotransmitter systems, may cause olfactory impairment, which may contribute to cognitive and memory decline during aging and NDs, such as AD and PD. Aging-related OE integrity loss can be brought on by hereditary factors, airborne pollutants, smoking, and receptor cell loss of sensory responses. A paired helical tau components were found in the OE of AD patients, according to immunohistochemical investigations. The Bloodcerebrospinal Fluid Barrier (BCSFB), the olfactory and trigeminal nerves, as well as the BBB and BBB can all allow microbial infections to reach the Central Nervous System (CNS). Endothelial and choroid plexus epithelial cells compose the BCSFB, which generates CSF. The pathogens use the Trojan-horse technique to pass through the BBB either transcellular, paracellularly, or with the assistance of infected phagocyte. To cause increased permeability, encephalopathy, or pleocytosis, the pathogens disrupt the BBB's normal functioning [7]. Chronic inflammation and CRS disrupt the local microbiota's balance, which may contribute to the onset of AD and dementia. Three factors—odor threshold, odor discrimination, and odor identification using the Sniffin' Sticks test—were used by Hedner et al. to examine the olfactory dysfunctions about cognitive demands. The odor representation is retained in long-term memory, making the odor tests successful. The brain can therefore later reveal and retrieve the odor. The sense of smell aids in decision-making, eating, recognizing danger, and other actions. It also aids in the perception of the surrounding environment. Neurological problems frequently result in anosmia, which is the full absence of olfactory function, and hyposmia, which is a decline in olfactory function. Other causes of anosmia or hyposmia include head trauma, cranial surgery, allergies, medicine, cranial surgery, Upper Respiratory Tract Infections (URTIs), and chemicals that irritate the nose. According to the pertinent studies that are now available, olfactory and memory deficits are common in NDs like AD, PD, MS, Huntington's disease, and motor neuron disease. Studies have looked at the connection between Chronic Rhinitis (CR) and dementia, and CR has also been linked to stroke, vasculopathy, and vascular dementia. People with CR who also had mild cognitive impairment were more likely to acquire dementia than patients without CR. It is possible to think of chronic inflammation as the connecting element between CR and AD. In CR, inflammation is started by an immune system that is dysregulated. A decrease in immunoglobulin J chain, antileukoproteinase, and surfactant protein A and an increase in immune cells, eosinophils, and basophils [8], is associated with the pathology of CR. These immune cells produce inflammatory cytokines such as IL-13, IL-5, IL-4 , IL-6, IL-12, IL-18, Tumor Necrosis Factor (TNF), and transforming growth factor (TGF-β) in the mucosal region of CR patients. Therefore, the rise in inflammatory cytokines, which impairs the regeneration of nasal epithelial cells by preventing the proliferation of neural progenitor cells and inducing CR, may also result in the destruction of neural integrity in the CNS and result in dementia. The olfactory neuronal epithelium is harmed as CR disease worsens with age. The hallmark symptoms of AD include memory loss and cognitive deficits. Due to the significant risk of AD in the elderly, the primary cause of dementia has drawn attention from all over the world. The early signs of AD are depression and cognitive impairment, which thereafter result in significant memory loss, behavioral and personality changes, challenges carrying out daily chores, decreased communication abilities, compromised immunological function, and challenges with movement and swallowing [9]. The relationship between AD pathology and the inflammatory responses of the nasal microbiota is currently unsupported by direct evidence. However, in certain instances, sinus therapy and CR treatments were able to ameliorate cognitive impairment. C. pneumonia was also discovered in the microglia, astrocytes, and neurons of patients who passed away from AD in addition to OB infections. As a result of C. pneumonia invasion, the defense capabilities of astrocytes and microglia cells have declined, which may further exacerbate AD pathogenesis. One of the causes of mortality in AD patients has been the pneumonia-causing bacterium C. pneumonia. These results confirm the role of respiratory infections in the development of AD. One of the biomarkers of physiological deterioration, heart failure, stroke, diabetes, hypertension, liver damage, and even cancer is olfactory dysfunction. Olfactory dysfunction is also predicted to be a high-risk marker for psychosis and other neurological diseases, such as MS and epilepsy. Pathogens can enter the body through the mouth and nose, where they can then spread to the CNS and cause PD pathogenesis. It has been investigated how the nasal microbiome and PD are related. The link between PD and nasal microbiota has been examined. The results indicated that the dysbiosis of the nasopharyngeal microbiota creates an inflammatory response to α-synuclein that ends in neurodegenerative disorders. The accumulation and aggregation of αsynuclein in the dopaminergic substantia nigra of the CNS cause a neuronal loss in PD. Most PD patients showed olfactory deficits in the early period of the disease before the occurrence of motor symptoms. Clinically, PD patients experience Non-motor Symptoms (NMS), such as decreased salivation, drooling, dysphagia, and hyposmia. These NMS are related to pathological changes in the olfactory system. These studies suggested the involvement of the nasal microbial community in the progression of PD [10].

 

Discussion

Either as opportunistic pathogens or commensals, microbes can thrive inside the host. The microbes are protected by the mucosal membranes, and the microbiota is engaged in several processes, including metabolism, immunological responses, and disease resistance. To retain a healthy microbiome, mucosal habitats must be kept in good condition. By modifying the physiology of the olfactory epithelium, the nasal microbiota may be related to olfactory function. Due to the loss of olfactory NE and the decreased activity of the olfactory cortex, olfactory impairment is more common as people age. Olfactory impairment may result from respiratory illnesses. Once inside the nasal canal, the invading pathogens attach to the olfactory receptors of the olfactory NE. They may cause olfactory dysfunction, inflammatory changes, and possibly temporary or permanent olfactory impairment. Diet has a lasting impact on how the human microbiota develops and how the host and mucosal environments interact with the microbiota. Whether or whether the microbiota is involved, dietary changes have an impact on the mucosal barriers. Lipids, proteins, and carbohydrates in the diet may differentially control the amount of microbiota in the body. A fiber-rich diet can reduce the gut microbiota's ability to produce inflammatory cytokines. To keep the gut operating normally during a respiratory illness, a healthy microenvironment must be maintained. Globally, the rise in respiratory, inflammatory, and neurological conditions has posed a more serious health hazard. Numerous research has explained the nasal-gut microbiota's role in inflammatory disorders, however, the cause of neurological diseases is not well understood. Therefore, more research is required to clarify the relationship between the neurological system and the nasal microbiota.

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