Oral Microbiota: A Key Player in Weight Control?

The oral microbiota is not simply composed of bacteria but represents a complex and dynamic ecosystem that includes a diverse array of microorganisms such as bacteria, archaea, fungi, viruses, and protozoa [1]. This intricate community colonizes various distinct niches within the oral cavity, including the cheek, lip, teeth, gingival sulcus, attached gingiva, tongue, hard palate, and soft palate, with each site harboring a unique composition of microbial species [1]. While our understanding of this diverse ecosystem is growing, the majority of existing research has primarily focused on the bacterial components of the oral microbiota, often utilizing 16S rDNA sequencing techniques [2]. This methodological bias highlights a current limitation in the field, underscoring the need for further investigation into the roles played by fungi, viruses, and protozoa in the context of the oral microbiota–brain axis (OMBA) to gain a more comprehensive understanding of their collective influence. External factors, particularly diet or processed food combined with antibiotics and sanitation, significantly influence the diversity and composition of the microbial communities residing in the oral cavity [3]. For instance, a diet high in sugars and refined carbohydrates is known to promote the growth of cariogenic bacteria, such as Streptococcus mutans [3]. The development of cancers and systemic diseases has been implicated in the oral microbiota [3]. Conversely, the consumption of fermented foods and probiotics has been shown to enhance oral microbial diversity, which is generally associated with a healthier oral environment.

Oral microbiota ranks as second most diverse microbiota in human body with over 700 different bacterial species identified so far naturally [4]. This dynamic ecosystem harbors myriad bacterial phyla including Firmicutes and Proteobacteria alongside Euryarchaeota and Spirochaetes with Actinobacteria present too. Gram-positive and Gram-negative genera thrive prominently in a healthy mouth [1]. Abiotrophia, Peptostreptococcus, Streptococcus and Stomatococcus play pivotal roles amongst various Grampositive cocci normally found in diverse human flora. Species like Streptococcus sanguinis and Streptococcus salivarius exhibit notable prowess in synthesizing antimicrobial molecules that bolster defense of oral tissues against erosion [5]. Functions of each bacterium within this complex network remain largely shrouded in mystery still being slowly unraveled.

Gram-positive rods including Actinomyces and Bifidobacterium, Corynebacterium, Eubacterium, Lactobacillus, Propionibacterium, Pseudoramibacter, and Rothia are key contributors to oral microbial milieu. Actinomyces naeslundii can utilize urea as nitrogen source and resists acidic conditions pretty adeptly in mouth environments ordinarily. It assumes a predominant role amongst dental plaque bacteria thereby deeply influencing ecology of plaque in various significant ways suddenly nowadays [6]. Lactobacillus and Bifidobacterium alongside Streptococcus and Weissella are deemed beneficial probiotics for managing periodontal diseases and enhancing overall oral health significantly [7]. Gram-negative cocci like Moraxella and Neisseria are found in healthy mouths alongside Veillonella in quite diverse oral ecosystems normally. Various Gram-negative rods like Campylobacter, Capnocytophaga, Desulfobacter, Desulfovibrio, Eikenella, Fusobacterium, Hemophilus, Leptotrichia, Prevotella, Selemonas, Simonsiella, Treponema, and Wolinella are found pretty frequently [8]. Several microorganisms form biofilms remarkably well under certain conditions and with great tenacity. Fusobacterium nucleatum brings disparate bacteria together, substantively building structured biofilm communities and subsequently bolsters maturation of those biofilms rather markedly. Prevotella species residing in biofilm exhibit fascinating functionality, influencing their tenure in mouths and subtly interacting with the host immune systems indirectly. Prevotella typically tolerate oxygen fairly well, but their ability to thrive in such environments heavily relies on coaggregation with F. nucleatum. F. nucleatum, meanwhile, is found throughout various oral and gut environments, thriving in diverse ecological niches [9]. This symbiotic relationship fosters biofilm integrity and enables Prevotella to successfully persist within a diverse microbial consortium [10]. Further scientific investigation into the roles of various bacterial genera within the oral microbiome remains a promising area, deserving thorough exploration.

The specific roles of each bacterial genus within the oral microbiome remain a rich area for further scientific investigation. The predominant focus of current research on the bacterial components of the oral microbiota might be providing an incomplete picture of the OMBA’s influence on brain health [11]. Fungi constitute a relatively tiny fraction barely 0.1 percent of microbial life found lurking deep within oral cavities normally [12]. Species from genus Candida are most common among them while other notable fungi present include those from Cladosporium, Aureobasidium, Saccharomycetales, Aspergillus, Fusarium, and Cryptococcus [13]. Oral fungi can drastically influence immune function or sometimes cause opportunistic infections when host immune defenses are badly compromised [14]. Fungi and bacteria interact in complex ways playing somewhat surprisingly a crucial albeit often overlooked role in shaping oral microbiota. Fungi like Candida facilitate bacterial adherence onto their surfaces and epithelial cells yielding distinct microbial communities around covered and bare cells [15]. Bacterial resistance gets enhanced remarkably by such relationships and diversity of oral microbiome gets influenced substantially by them. The oral cavity harbors a complex ecosystem beyond just bacteria, and the interactions between these different microbial groups could be crucial in mediating communication with the brain. Future studies that incorporate the roles of fungi, viruses, and protozoa are essential for a more holistic understanding of the mechanisms involved in the OMBA.

The oral cavity serves as the primary entry point for both nutrients and microorganisms into the body, positioning it as a critical interface between the internal environment and the external world. Beyond its role in digestion, the oral cavity is also the site where flavor perception begins, involving a direct and rapid communication pathway with the brain [11]. This process is initiated when food is introduced into the mouth and chewing and salivation release taste and aroma compounds. These compounds then activate taste receptors, and the trigeminal nerve located within the oral cavity, as well as olfactory receptors in the nasal cavity, triggering a cascade of reactions that stimulate sensory neurons. These neurons subsequently transmit signals to the brain, where they are integrated in the cerebral cortex to create a comprehensive flavor perception in terms of quality, intensity, and hedonic value. These sensory signals also activate other brain regions involved in emotional responses and appetite regulation. The trigeminal nerve, specifically, plays a key role in this sensory signaling pathway, directly connecting the oral cavity to the brain. The everyday experience of flavor perception vividly illustrates the direct and rapid communication pathway between the oral cavity and the brain. This readily observable connection suggests that other, less obvious interactions mediated by the oral microbiota could also be highly significant in influencing brain function. The continuous exchange of sensory information between the mouth and the brain underscores the potential for microbes residing in the oral cavity to also engage in communication that impacts neurological processes.

CNS, including the brain, represents the ultimate target of the influence exerted by the oral microbiota through the OMBA. While the brain is protected by the highly selective blood-brain barrier (BBB), which restricts the passage of many substances from the bloodstream, this barrier can be compromised under certain conditions. Such breaches in BBB integrity can potentially allow microbial components, including whole microorganisms and their metabolites, to enter the brain parenchyma. The brain plays a critical role in integrating sensory information from the oral cavity, as evident in flavor perception, and it also influences systemic processes like appetite and emotional responses. Importantly, oral microbes and their various metabolic products have the potential to disrupt normal neurological functions and even cause damage within the brain.

Despite the protective function of the BBB, its potential vulnerability suggests that mechanisms exist for oral microbial components to potentially reach and interact with brain tissue. Understanding the specific conditions under which the BBB’s integrity is compromised in the context of oral dysbiosis is crucial for elucidating the pathways through which the OMBA can impact neurological health. Factors such as inflammation, infection, and aging can affect BBB permeability, potentially facilitating the entry of oral microbial elements into the brain.

Recognizing the interconnectedness of the oral cavity, the gut, and the brain through their respective microbial communities, the concept of the oral-gut-brain axis has emerged [16]. This framework emphasizes the intricate interactions between these three components and highlights the potential for disruptions in one area to impact the others. For instance, poor oral hygiene and untreated oral diseases can lead to an overgrowth of harmful oral bacteria. These pathogenic microbes can then translocate to the gut and/or directly influence the brain, potentially leading to a range of deleterious systemic effects that can lead to oral infectious diseases (caries, periodontal and candidiasis), certain cancers, hypertension, rheumatoid arthritis, systemic lupus erythematosus, and Alzheimer’s disease and mental health disorders [16, 17].

The oral-gut-brain axis framework provides a holistic perspective on how oral health can influence both gut and brain health. It suggests that interventions aimed at improving oral health, such as maintaining good oral hygiene and adopting appropriate dietary practices, could have beneficial effects that extend beyond the oral cavity to positively impact both the gut microbiota and brain function. This integrated view is essential for understanding the complex interplay between microbiota and neurological wellbeing.

While the oral and gut microbiota are interconnected through microbial transmission, they also maintain distinct compositions and perform unique functions within the host [18]. This raises the question of whether their effects on the brain are synergistic, meaning they work together to produce a combined effect greater than the sum of their individual effects, or if they exert independent influences on brain function [19]. It is also possible that their interactions with the brain involve a combination of both synergistic and independent mechanisms. Further research is needed to fully disentangle these complex relationships. Notably, diet can influence microbial diversity in both the oral cavity and the gut. However, some dietary components may have differential effects on these two microbial communities. For example, fermentable carbohydrates can serve as prebiotics that promote the growth of beneficial gut bacteria while simultaneously contributing to the growth of harmful oral bacteria [3]. This highlights the complexity of the interplay and the need for nuanced approaches when considering dietary interventions.

Determining whether the oral and gut microbiota influence the brain through independent pathways or via synergistic interactions is a key area for future investigation. Surprisingly, several murine models of gastrointestinal and neurodegenerative diseases showed gut commensal bacterial translocation to the brain, associated with markers of neuroinflammation and neural protein aggregate formation, suggesting a potential relationship between neurological diseases [20]. Understanding the nature of this interplay is crucial for developing targeted therapeutic interventions that consider the microbiota as a whole, rather than focusing solely on either the oral or the gut component for reversing these diseases [3, 11, 19]. Elucidating these complex interactions will provide a more complete picture of the microbiota-brain axis and its implications for health and disease.

While the gut microbiome has garnered significant attention for its role in obesity and metabolic health, emerging evidence increasingly highlights the intricate connection between the oral microbiota and weight control, particularly in obese individuals. The oral cavity, hosting the second largest microbial community in the human body, is not merely a gateway for food but a dynamic ecosystem whose balance can influence systemic health, including metabolic regulation [21].

Numerous studies have identified significant differences in the composition and diversity of the oral microbiome between normalweight individuals and those with obesity. Obese individuals often exhibit [22]:

• Altered microbial diversity: This can include a reduced diversity in some cases, suggesting a less robust and adaptable microbial community.

• Shifts in dominant phyla: Similar to the gut, an increased abundance of Firmicutes and a higher Firmicutes/ Bacteroidetes ratio have been observed in the oral cavity of obese individuals [23].

• Enrichment of specific pathogens: Bacteria associated with periodontal disease, such as Porphyromonas gingivalis, Filifactor alocis, and certain Prevotella species, are often found in higher proportions in obese individuals, even in the absence of overt clinical periodontitis. This reflects the well-established bidirectional link between periodontitis and obesity [24].

The mechanisms by which the oral microbiota might influence weight control are multifaceted and are an active area of investigation:

Impact on Taste Perception and Food Preference:

• Oral bacteria can directly influence taste bud function and density, potentially altering taste perception.

• An obesity-associated oral microbial signature may contribute to the commonly observed reduced taste perception in obese individuals, potentially driving increased food consumption and caloric intake to compensate.

• Microbial metabolites produced in the mouth might also interact with taste receptors or influence central nervous system pathways related to appetite.

Modulation of Systemic Inflammation:

• Oral pathogens, particularly those involved in periodontal disease, can contribute to low-grade systemic inflammation. This involves the release of pro-inflammatory cytokines (e.g., TNF-α) from diseased periodontal tissues, which can then circulate throughout the body.

• Chronic systemic inflammation is a key characteristic of obesity and metabolic syndrome, contributing to insulin resistance and adipose tissue dysfunction. Thus, an inflammatory oral microbiome could exacerbate or even contribute to the metabolic dysregulation seen in obesity.

Influence on the Gut Microbiome (Oral-Gut Axis):

• Bacteria from the oral cavity can be constantly swallowed, influencing the composition and function of the gut microbiome.

• Oral dysbiosis could lead to the translocation of specific oral bacteria to the gut, potentially disrupting the delicate balance of the gut microbiota and contributing to gut dysbiosis.

• This “oral-gut axis” suggests that changes initiated in the mouth can have downstream effects on energy metabolism, nutrient absorption, and inflammation mediated by the gut microbiota.

Direct Metabolic Effects:

• Some oral bacteria might directly contribute to increased metabolic efficiency, leading to more effective energy extraction from food.

• Hypotheses also suggest that certain oral bacteria could increase appetite, though direct evidence for this in humans is still limited.

• Furthermore, specific oral bacteria might redirect energy metabolism by facilitating insulin resistance through their inflammatory byproducts or by reducing levels of beneficial adipokines like adiponectin.

Understanding the intricate interplay between the oral microbiota and weight control opens new avenues for research and potential therapeutic interventions. While still in its early stages, this research suggests that:

• Oral hygiene interventions: Maintaining good oral hygiene and managing oral diseases like periodontitis might have beneficial systemic effects on weight control and metabolic health.

• Targeting specific oral bacteria: Future research may explore strategies to modulate the oral microbiome, perhaps through probiotics, prebiotics, or targeted antimicrobial approaches, to influence weight management in obese individuals.

• Biomarkers for obesity: Specific oral bacterial signatures, such as the presence of Selenomonas noxia at certain levels, have been identified as potential indicators of overweight conditions, suggesting a diagnostic role for the oral microbiome.

The oral microbiota is far from a passive bystander in the complex etiology of obesity. Its dynamic composition, direct and indirect metabolic influences, and interconnectedness with the gut microbiome position as a significant, though still largely understudied, player in weight control and overall metabolic health in obese individuals. Continued research in this area holds promise for developing novel, patient-oriented therapeutic and preventative strategies.

None.

No conflict of interest.

1. Vinicius Goncalves Maltarollo (2024) Computer-Aided and Machine Learning-Driven Drug Design From Theory to Applications, Springer Publication.
2. Inamuddin, Tariq Altalhi, Jorddy N Cruz, Moamen Saleh El Deen Refat (2022) Drug-Design-using-Machine-Learning, Wiley Publication.
3. Nathan Keighley (2025) Introduction to organic and Medicinal Chemistry, CRC Press.