The human adult gut harbors a highly diverse microbial community, with microbial density (microbiota per gram) varying across different regions of the gastrointestinal tract: the stomach (10¹), duodenum (10³), jejunum (10⁴), ileum (10⁷), and colon (10¹²) [38, 39]. However, it is crucial to note that approximately 70% of the microorganisms in the gut are not culturable, necessitating the use of molecular sequencing techniques to study this complex microbiome [40]. While the composition and diversity of the gut microbiome vary across these regions, research typically focuses on fecal samples, which are most closely associated with the colon and are easier to analyze. The gut microbiome consists of various microbial taxa, including archaea, bacteria, fungi, protozoa, and viruses, with bacteria being the most dominant group [29]. The human gut is predominantly colonized by several bacterial phyla, including Verrucomicrobiota, Bacillota, Campylobacterota, Actinomycetota, Fusobacteriota, Bacteroidota, Thermodesulfobacteriota, and Pseudomonadota [27, 29, 38, 41]. The distribution of microorganisms across different parts of the intestines has been the subject of considerable research. Studies on the upper gastrointestinal tract have identified Actinomyces, Fusobacterium, Gemella, Neisseria, Prevotella, Pseudomonas, Streptococcus, and Veillonella as the most prevalent bacterial genera [42]. In contrast, the lower gastrointestinal tract exhibits a distinct microbial profile, with genera such as Bacillus, Exiguobacterium, Lysinibacillus, Oceanobacillus, Paenibacillus, and Solibacillus being more abundant in the duodenal mucosa [43]. In the jejunum and ileum, common bacterial genera include Enterococcus, Escherichia, and Lactobacillus in the jejunum [44], and Clostridium, Escherichia, and Streptococcus in the ileum [45]. Finally, the colon is predominantly populated by genera such as Bacteroides, Coprobacillus, Enterococcus, and Escherichia/Shigella [46].

Increasing evidence indicates that the gut microbiome may play a central role in modulating behavior and brain function via multiple mechanisms, including the production of neurotransmitters such as γ-aminobutyric acid (GABA), dopamine, kynurenic acid, and serotonin, as well as a range of metabolites derived from microbial activity, such as BAs, SCFAs, D-amino acids, and tryptophan catabolites [14–16]. In this context, research has consistently shown a link between changes in the composition and diversity of the gut microbiome and the development of psychiatric and brain-related conditions, including various NDDs [47–52].

In the case of AD, Bostanciklioğlu [53] proposed three distinct mechanisms linking the gut microbiome to the pathogenesis of AD. These mechanisms include: (i) CNS inflammation and cerebrovascular degeneration induced by bacterial metabolites and amyloids; (ii) disruption of autophagy-mediated protein clearance due to an altered gut microbiome; and (iii) modulation of brain neurotransmitter levels via the vagal afferent pathway influenced by the gut microbiome. Research has shown that several bacteria, such as Bacillus subtilis, Escherichia coli, and Salmonella enterica serovar Typhimurium, are capable of producing amyloid fibers [54]. Interestingly, while microbial amyloids share tertiary structural similarities with human CNS amyloids, they act as prion-like agents through molecular mimicry, leading the amyloidogenic protein to adopt a pathogenic β-structure [55, 56]. In elderly individuals, these bacterial amyloid fibrils have been observed to cross both the intestinal barrier and the BBB, promoting an increase in Aβ accumulation in the brain and amplifying the inflammatory responses to cerebral amyloids, such as Aβ and α-synuclein [57]. In addition, the presence of bacterial lipopolysaccharides in the brain has been noted, suggesting that these bacterial components might play a role in AD development. It is hypothesized that lipopolysaccharides can cross both the intestinal tract and the BBB, where they interact with microglial TLR4-CD14/TLR2 receptors, leading to increased Aβ levels through elevated cytokine production [58]. Furthermore, Aβ1–42, which is a TLR4 agonist, has been shown to stimulate NFκB-mediated cytokine production, which in turn raises Aβ levels, damages oligodendrocytes, and contributes to the myelin degeneration observed in AD [59]. Elevated secondary BAs have also been linked to Aβ production and accumulation by disrupting the cholesterol metabolic pathway [60]. Moreover, the by-products of gut microbiome dysbiosis can influence the expression of genes and synaptic proteins involved in neuroinflammation, leading to the accumulation of inflammatory proteins in the brain, activation of astrocytes, neuronal apoptosis, and microglial inflammatory responses [61–63].

Despite the presence of inter- and intra-individual variability, as well as factors such as gender, diet, and geographic location, a substantial proportion of AD patients exhibit a distinct gut microbiome profile compared to age-matched healthy individuals [64]. A meta-analysis that included both discovery and replication cohorts confirmed a significant association between 20 specific bacterial genera and AD [65]. Notably, two bacterial species, Collinsella spp. and Veillonella spp., were strongly linked to the APOE rs429358 risk allele, whereas Eubacterium fissicatena was associated with a protective factor against AD. These results indicate that host genetic factors may play a substantial role in determining the abundance of specific bacterial genera, which could serve as potential biomarkers or therapeutic targets for AD [65]. Furthermore, meta-analytic data show that, regarding the phylum level, Bacillota are considerably reduced in AD patients in comparison with healthy controls, while Bacteroidota are significantly elevated in individuals with mild cognitive impairment compared to controls [66].

A substantial proportion of patients with PD exhibit gastrointestinal symptoms, including constipation, long before the appearance of motor deficits. This observation suggests a potential link between changes in gut motility and gut microbiome dysbiosis. The protein α-synuclein, which aggregates in the brains of individuals with PD to form Lewy bodies, has also been found to aggregate in the enteric nervous system [67]. Current hypotheses propose that the pathological α-synuclein could begin in the gut and later propagate to the brain through the vagus nerve, thereby contributing to PD pathogenesis [47, 49, 68, 69]. Tansey et al. [70] suggested that gene-environment interactions, combined with an aging immune system, may promote the development and progression of PD. Although several studies have linked gut microbiome dysbiosis to the pathogenesis of PD [71, 72], there is limited research on how the fecal microbiota is altered in PD patients with cognitive impairment. Wallen et al. [73] identified three distinct microbial clusters associated with PD: Cluster 1 consisted of opportunistic pathogens, all of which were more abundant in PD; Cluster 2 included SCFA-producing bacteria, all of which were less abundant in PD; and Cluster 3 contained carbohydrate-metabolizing probiotics, which were more abundant in PD. At the genus level, Bifidobacterium, Corynebacterium, Lactobacillus, Porphyromonas, and Prevotella were found to be more prevalent in PD patients compared to controls, while Agathobacter, Blautia, Butyricicoccus, Faecalibacterium, Fusicatenibacter, Lachnospira, Oscillospira, and Roseburia were less abundant. In a meta-analysis of PD patients from five countries, Hirayama and Ohno [74] reported that the Akkermansiaceae and Lactobacillaceae families were dominant in the gut microbiome of PD patients, with Akkermansia and Christensenella (formerly Catabacter) being the most prominent genera. In contrast, Faecalibacterium and Roseburia genera, together with the Lachnospiraceae family, were found to be reduced in PD patients. The reduction of SCFA-producing bacteria and the increase in mucin-degrading bacteria observed in PD may lead to increased intestinal permeability, potentially allowing toxins like lipopolysaccharides to reach the intestinal neural plexus. This could contribute to the abnormal accumulation of α-synuclein fibrils, further exacerbating PD pathology.

HD is an inherited neurodegenerative disorder characterized by progressive motor decline, cognitive dysfunction, and neuropsychiatric symptoms. This condition results from the age-dependent expansion of cytosine-adenine-guanine (CAG) repeats in the IT15 gene [75], leading to the production of a polyglutamine-expanded, nonfunctional huntingtin protein. The accumulation of this protein has been shown to form aggregates that ultimately cause neuronal damage [76]. The neuronal loss associated with these protein aggregates disrupts various physiological processes. Research indicates that HD is linked to impaired communication, organizational skills, and cognitive decline. These impairments can lead to a range of adverse outcomes, such as dementia, depression, and suicidal tendencies [77]. Beyond cognitive, motor, and neuropsychiatric symptoms, which are closely tied to brain changes, individuals with HD also experience a variety of gastrointestinal issues, including diarrhea, nutrient deficiencies, gastritis, and unintentional weight loss. These gastrointestinal disturbances are considered clinical features of the disease [51]. Although much of the research on HD pathogenesis has focused on brain atrophy and its associated cognitive, behavioral, and psychiatric symptoms, the role of peripheral pathology, particularly in the gut, in relation to the core symptoms of HD remains underexplored [78]. Mukherjea et al. [79] suggested that the gut microbiome in HD patients may present an increase in genera such as Akkermansia and Intestinimonas, whereas the Lachnospiraceae family and the Butyrivibrio genus are typically decreased. Figure 1 presents a hypothetical representation of microbial features associated with gut microbiome dysbiosis in the context of NDDs.

Table 1 provides an overview of studies exploring the relationship between gut microbiome dysbiosis and the clinical pathophysiology of NDDs, thereby summarizing alterations in specific bacterial taxa and their reported effects on disease-related processes.

The oral microbiome refers to the diverse community of microorganisms residing in the human oral cavity, constituting the second-largest microbial ecosystem in the human body. This microbiome includes a wide range of microorganisms, such as archaea, bacteria, fungi, protozoa, and viruses [81, 82]. Bacteria dominate the oral microbiome in terms of both abundance and variety. The major bacterial phyla in the oral cavity include Actinomycetota, Bacillota, Bacteroidota, Fusobacteriota, Pseudomonadota, and Spirochaetota [83]. In addition, several minority and candidate phyla have been identified, including Gracilibacteria (GN02/BD1-5), SR1, Chloroflexota, Saccharibacteria (TM7), Chlorobiota, WPS-2, and Synergistota [81]. Cho et al. [84] suggested categorizing the oral cavity into three separate metaniches. In this respect, the P-GCF metaniche includes the bacterial genera that are present in both the gingival crevicular fluid and the supragingival dental plaque. This niche is primarily populated by Aggregatibacter (Pseudomonadota), Actinomyces and Corynebacterium (Actinomycetota), Fusobacterium and Leptotrichia (Fusobacteriota), and Capnocytophaga and Tannerella (Bacteroidota). The S-T-HP metaniche, consisting of the bacterial communities on the tongue, saliva, and hard palate, is mainly dominated by Alloprevotella, Porphyromonas, and Prevotella (Bacteroidota), Granulicatella and Veillonella (Bacillota), and Neisseria (Pseudomonadota). Lastly, the U-C metaniche, covering the cheek and sublingual area, is predominantly populated by Actinobacillus and Haemophilus (Pseudomonadota), and Gemella and Streptococcus (Bacillota). In contrast, Li et al. [85] proposed a different distribution of the oral microbiome into three principal niches: soft tissue surfaces, tooth surfaces, and saliva, which comprise the buccal mucosa, palate, tongue, and gingiva. In a study of the salivary microbiota within the context of a Qatari population, it was noted that the most prevalent genera were Prevotella, Haemophilus, Gemella, Neisseria, Porphyromonas, Veillonella, and Streptococcus [86]. However, research on the salivary microbiota of a Japanese cohort found a predominance of Rothia mucilaginosa, Streptococcus salivarius, Granulicatella adiacens, Streptococcus mitis, and Neisseria flavescens [87]. Such variations in microbial composition can be influenced by a range of factors, including environment, diet, and genetic predispositions [88]. In this context, the tooth surface offers an optimal niche for bacterial proliferation and the establishment of dental plaque. Research shows that dental plaque generally exhibits higher microbial richness, α-diversity, and greater uniformity when compared to microbial samples from the tongue or saliva [89]. Anaerobic bacteria such as Veillonella, Fusobacterium, and Actinomyces are particularly abundant in subgingival plaque [82]. The composition of the microbial community on tooth surfaces is also influenced by the anatomical and physiological characteristics of the tooth surfaces and the perigingival area. For instance, Streptococcus species are commonly found on the labial surfaces of canines and incisors, but are less frequently observed on the lingual surfaces [90]. The tongue, in contrast, supports a more diverse and denser microbial community compared to other mucosal areas [91]. Facultative and obligate anaerobes, including Veillonella, Streptococcus, Actinomyces, Neisseria, Haemophilus, Leptotrichia, Prevotella, and Porphyromonas, are the predominant microorganisms found on the tongue [89].

Given that the oral cavity is the primary gateway to the human body, alterations in the oral microbiome may play a role in the onset and progression of neuropsychiatric conditions, including NDDs [92, 93]. Research has linked specific oral microbiome profiles with individuals suffering from brain-related conditions, giving rise to the hypothesis that a relationship exists between these two elements. Specifically, this hypothesis proposes that the CNS may influence the oral microbiome, promoting the growth of certain microbial populations. Similar to the effects observed in the gastrointestinal tract, this phenomenon has been observed in patients with mental health disorders, who often demonstrate poor oral health [94]. Consistent with this, further evidence supports a link between the oral microbiome, oral diseases, and various NDDs, including AD and PD [95].

It has been suggested that the oral microbiome influences brain function through various direct and indirect mechanisms. One direct route involves the transmission of microbial material to the brain through the olfactory and trigeminal nerve pathways, which connect the oral cavity to the olfactory bulb [96]. Chronic oral conditions can compromise the oral mucosal barrier, permitting bacterial lipopolysaccharides and microorganisms to enter the circulation, frequently via mechanical actions like chewing or brushing. This process elicits a strong inflammatory response by stimulating endothelial cells expressing TNF-α and IL-1β receptors, which subsequently signal perivascular macrophages. In turn, these signals facilitate neuroinflammation and activate the hypothalamic-pituitary-adrenal (HPA) axis [81, 97]. Moreover, these inflammatory mediators can disrupt the BBB, a condition linked to inflammation and cognitive decline in NDDs [98]. Porphyromonas gingivalis, a key bacterium associated with periodontitis, has been shown to breach the BBB and colonize the brain, where it produces cysteine proteases (i.e., gingipains). These gingipains interfere with the metabolism of the transmembrane protein β-amyloid precursor protein (APP), which is crucial for neuronal development and synaptic stability [99, 100]. In turn, the oral microbiome could also influence brain activity in an indirect way via the oral-gut-brain axis [101]. Research has demonstrated that oral microbiome bacterial species can be transported to the gut via saliva, where they alter the composition of the gut microbiome [102]. As a result, the oral cavity may serve as a reservoir for pathogenic microorganisms that typically reside in the gut, triggering immune responses in the gut and inducing persistent inflammation [102].

Several studies have indicated a potential link between periodontal disease, oral malodor, cognitive decline, and an increased risk of developing AD [103, 104]. In this context, P. gingivalis has been demonstrated to trigger the accumulation of neurofibrillary tangles (NFTs) and Aβ plaques after inducing oral infection in murine models. In addition, research indicates that administering gingipain inhibitors orally can reduce P. gingivalis levels and decrease Aβ42 production in neural tissues of mice [105]. Additional research has demonstrated that chronic systemic P. gingivalis infection leads to Aβ accumulation in human models, specifically in the neuroblastoma cell line SH-SY5Y [106]. Moreover, intraperitoneal injection of P. gingivalis lipopolysaccharides into male C57BL/6J and SAMP8 murine models led to diminished neprilysin expression within the hippocampus [107]. In turn, reduced neprilysin levels have been linked to heightened Aβ accumulation, which constitutes a hallmark of AD [108]. The oral bacterium Aggregatibacter actinomycetemcomitans has also been associated with AD due to its capacity to trigger inflammatory responses, affect the CNS, and promote the release of Aβ [109]. Furthermore, A. actinomycetemcomitans has been found to elevate the production of inflammatory cytokines and Toll-like receptors in brain cells, leading to the increased expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β [110]. Other bacterial species, including Fusobacterium nucleatum and Treponema denticola, have also been linked to AD in mouse models [111, 112].

Recent research emphasizes the possible involvement of the oral microbiome in the context of PD [113]. In fact, correlations have been identified between specific bacterial genera present in the oral cavity and the severity of depressive and anxious symptoms in individuals with PD, indicating that the oral microbiome may influence the psychiatric symptoms associated with PD [114]. In a separate preclinical study, periodontitis induced by ligatures, involving subgingival plaque, was shown to worsen motor dysfunction, dopaminergic neuron degeneration, and microglial activation in mice with PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [115]. This investigation revealed that the oral pathogens Veillonella parvula and Streptococcus mutans necessitate the presence of periodontitis to exacerbate motor dysfunction and neurodegeneration in MPTP-treated mice with PD. The observed effects were associated with microglial activation and the infiltration of T helper 1 (Th1) cells in the colon, ileum, brain, and cervical lymph nodes of the mice. Furthermore, neutralizing interferon-gamma (IFN-γ) showed protective effects on dopaminergic neurons in mice with PD that were treated with V. parvula and S. mutans. Figure 2 presents a hypothetical representation of the relationship between oral microbiome dysbiosis and NDDs.

Various pathological conditions can compromise the integrity of the oral-gut barrier, substantially increasing the risk of translocation and colonization by oral-derived microorganisms [116]. Impairments in mucosal defenses, influenced by host-associated factors such as aging and poor oral hygiene, facilitate the migration of microorganisms, while pharmacological interventions, including antibiotics, can downregulate the expression of key barrier proteins such as mucin 2, zonula occludens-1, and occludin. This disruption of the epithelial barrier, together with thinning of the mucus layer, enhances bacterial translocation and may promote the overgrowth and intestinal colonization of oral pathogens, including Streptococcus spp. and P. gingivalis [117]. Similarly, proton pump inhibitors increase gastric pH by reducing acidity, thereby allowing oral bacteria such as Rothia spp. and Streptococcus spp. to survive passage through the gastrointestinal tract [118]. Chronic oral infections, particularly periodontitis, maintain a persistent microbial load in the oral cavity, and pathogens such as P. gingivalis and Klebsiella spp. can reach the gastrointestinal tract via oral or hematogenous routes, contributing to dysbiosis and intestinal inflammation [119]. In addition to direct translocation, some oral bacteria can exploit host immune cells to disseminate systemically, a mechanism often described as a “Trojan horse”, with P. gingivalis serving as a well-characterized example of this immune-cell exploitation strategy capable of reshaping the microbial community [120].

The skin, as the largest organ in the human body, covers an average surface area of approximately 30 m² and supports a complex and diverse microbial community. Estimates suggest that an adult’s skin hosts from 10³ to 10⁶ microorganisms, depending on the specific area being sampled [121]. The dominant bacterial phyla in the human skin microbiome include Actinomycetota, Bacillota, Bacteroidota, and Pseudomonadota. The primary genera found on the skin are Acinetobacter, Cutibacterium, Corynebacterium, Micrococcus, Staphylococcus, and Streptococcus [122]. In addition, fungi from the Ascomycota and Basidiomycota divisions are integral members of the skin microbiome, with Malassezia being the most prevalent genus, including species such as M. sympodialis, M. globosa, and M. restricta [123]. The skin also harbors a variety of viruses, primarily from the families Circoviridae, Papillomaviridae, Poxviridae, and Polyomaviridae [124]. Furthermore, a number of bacteriophages have also been identified recently as part of the skin microbiome [125].

Recent research has suggested that the skin microbiome may play a role in neuropsychiatric conditions such as NDDs, potentially through its influence on the gut microbiome [126]. This raises the hypothesis that the skin microbiome could indirectly affect the gut-brain axis, contributing to brain functional activities [127]. This interplay might influence the development of NDDs through immune-related pathways [126], and might also involve mechanisms such as increased oxidative stress, DNA damage, epigenetic alterations, impaired cell signaling, and gut dysbiosis. However, research on changes in the skin microbiome of patients with brain-related conditions remains limited. In a recent study, Arikan et al. [128] identified an association between the axillary microbiota and cognitive impairment in PD patients, indicating a potential role of the skin microbiome in cognitive dysfunction. Evidence also suggests that the human skin microbiome can produce neurotransmitters, including trace amines, dopamine, and serotonin, which may modulate classical neurotransmitter signaling or activate trace amine-associated receptors [129]. In this context, Staphylococcus species have been identified as capable of neurotransmitter production, displaying two distinct profiles: one producing tryptamine and phenylethylamine, and the other tyramine and dopamine. These profiles are determined by two bacterial aromatic amino acid decarboxylases: SadA and tyrosine/tyramine decarboxylase [129]. Moreover, a large population-based study indicated that inflammatory conditions marked by systemic TNF-α activity, such as psoriasis, may increase the risk of AD, while treatment with anti-TNF-α agents seems to reduce this risk [130]. However, other investigations have reported no significant link between psoriasis and the likelihood of developing AD or dementia [131]. Nevertheless, further research with larger sample sizes is needed to confirm these findings.

The nasal cavity harbors a wide range of microorganisms that play a role in preserving the health of the nasal mucosa and aiding the overall function of the immune system [132]. The nasal microbiome is primarily composed of several key bacterial taxa, including Actinomycetota (e.g., Corynebacterium and Cutibacterium), Bacillota (e.g., Dolosigranulum, Peptoniphilus, Staphylococcus, and Streptococcus), and Pseudomonadota (e.g., Haemophilus and Moraxella) [132]. Nevertheless, the diversity and composition of the nasal microbiome differ considerably across individuals, shaped by factors such as genetics, environmental exposures, age, lifestyle habits like smoking, and drug use [34, 35].

Although olfactory deficits and related neuropathology are well-established in the early stages of PD, evidence supporting a contributing role of the nasal microbiome remains limited [133]. For instance, one study found no marked differences in the nasal microbiome of the middle meatus between individuals with PD and healthy controls [134]. However, this does not preclude the possibility of localized microbial variations near the olfactory neuroepithelium, given that microbial communities can differ across nasal regions [135]. In AD, olfactory impairment similarly emerges years before classic symptoms and may offer predictive value when considered together with apolipoprotein E4 status [136]. Neuroimaging research has revealed reduced volumes of the olfactory bulb and tract in affected individuals compared to controls, with these changes showing correlations with cognitive performance [137]. In addition, meta-analytic data suggest that infection with the respiratory pathogen Chlamydia pneumoniae is associated with an increased risk of developing AD [138].

Building on the aforementioned, it can be stated that the involvement of the nasal microbiome in neuropsychiatric disorders constitutes a developing area of research. It is thought that the nasal microbiome may impact the established gut-brain axis via several mechanisms, such as direct interactions with the olfactory system, modulation of immune responses, and the synthesis of metabolites or neurotransmitters capable of crossing the BBB [139]. Research indicates that aging has a notable effect on olfactory function, positioning it as a potential early marker for certain NDDs [37]. Indeed, olfactory dysfunction, including anosmia (i.e., complete loss of smell) and hyposmia (i.e., reduced smell sensitivity), is commonly observed in patients affected by these conditions [37, 133]. Despite a scarcity of direct evidence linking the nasal microbiome to NDDs, some research has explored its potential involvement in AD and PD [37, 140]. In this respect, evidence suggests a possible correlation between nasal microbial communities and the onset or progression of these conditions. In particular, due to the frequent occurrence of olfactory dysfunction in the early stages of PD, Lazarini et al. [141] proposed a hypothesis suggesting that the nasal microbiome could be involved in the accumulation of misfolded α-synuclein, which is a protein primarily found in olfactory sensory neurons (OSNs). Misfolded α-synuclein is a key component of Lewy bodies, which are neuronal inclusions characteristic of PD pathology. More specifically, the hypothesis suggests that chronic dysbiosis in the nasal microbiome could trigger local inflammation, which might exacerbate damage to OSNs and lead to the accumulation of misfolded α-synuclein. This process could then spread to the olfactory bulb, substantia nigra pars compacta, and potentially other regions of the brain, ultimately contributing to the motor, cognitive, and psychiatric symptoms seen in PD patients. Furthermore, research suggests that distinct nasal microbial compositions could be associated with variations in olfactory function and cognitive performance, with certain genera such as Corynebacterium linked to lower risk of cognitive impairment and to favorable immunoregulatory profiles [142]. Mechanistically, dysbiosis in the nasal microbiome may facilitate the upward spread of pathogenic or pro-inflammatory bacteria along the olfactory pathway, promoting microglial activation, BBB dysfunction, and propagation of neurotoxic protein aggregates, which constitute processes implicated in NDDs [140]. These inflammatory and neuroimmune perturbations are likely to impact the local microenvironment of the olfactory epithelium and olfactory bulb, which are key sites of adult neurogenesis, thereby potentially compromising the proliferation and differentiation of olfactory progenitor cells and impairing the plasticity and repair of the olfactory system [140, 143]. In turn, research using intranasal delivery of therapeutic cells indicates that substances administered via the nasal route can reach the olfactory bulb and other brain regions, supporting the notion that molecules, microbial metabolites, or inflammatory mediators originating in the nasal cavity can influence neural survival, regeneration, and functional integration [143]. Figure 3 presents a hypothetical representation of direct and indirect relationships between nasal microbiome dysbiosis and NDDs.