Exploring the Interplay: Oral–Gut Microbiome Connection and the Impact of Diet and Nutrition

Abstract

The intricate interplay between the oral and intestinal microbiota holds increasing fascination within the context of health and nutrition. Serving as the gateway to the gastrointestinal tract, the oral microbiota hosts a diverse array of microbial species that significantly influence well-being or contribute to various diseases. Dysbiosis in the oral microbiota has been linked to conditions such as dental caries, periodontal diseases, and systemic disorders, including diabetes, cardiovascular disease, obesity, rheumatoid arthritis, Alzheimer's disease, and colorectal cancer. This review aims to comprehend the nuanced relationship between oral and intestinal microbiotas, exploring the pivotal role of diet in developing strategies for wellness promotion and disease prevention. Drawing insights from a myriad of studies encompassing both animals and humans, we examine the implications of microbial dysbiosis and its impact on health. A bibliographic search of 78 scientific articles was conducted across PubMed Central, Web of Science, Scopus, Google Scholar, and the Saudi digital library from January 2000 to August 2023. Following a rigorous screening process, the full texts of selected articles were critically reviewed to extract relevant information. Articles not meeting the inclusion criteria—specifically focused on oral–intestinal microbiota interaction and diet and nutrition—were meticulously excluded. Diet emerges as a key player in influencing both oral and intestinal microbiotas. Various dietary components, such as fiber, prebiotics, probiotics, and bioactive compounds, have demonstrated significant effects on the diversity and function of microorganisms in these ecosystems. Conversely, diets high in processed foods, added sugars, and saturated fats correlate with dysbiosis and an elevated risk of oral and gastrointestinal diseases. Understanding the intricacies of this interaction is paramount for the development of innovative approaches fostering a balanced oral–gut microbiota axis and improving overall human health. The implications extend to preventive and therapeutic interventions, emphasizing the practical importance of unraveling these complexities for public health and clinical practice. This comprehensive review delves into the intricate relationship between gut and oral microbiota, shedding light on their roles in various diseases, particularly focusing on oral diseases. Key findings are summarized, and implications for future research and clinical practice are discussed. In conclusion, the review underscores the urgent need for special attention to key microbiota in developing targeted interventions for promoting oral and gut health.

Keywords

microbiota - oral health - gut microbiota - dysbiosis - diet - nutrition

Introduction

Human health and wellness are dependent on the trillions of microorganisms that make up the human microbiota.[1] Because of their roles in digestion, metabolism, and immune regulation in the human body, both the oral and gut microbiotas have received significant attention. Furthermore, there is mounting evidence that suggests a reciprocal relationship between the oral and gut microbial ecosystems.[2] [3] [4]

Diet, as a crucial environmental factor, has been widely noticed for its impact on human health. Our diet not only influences our nutritional status but also influences the wide range and functionality of our oral and gastrointestinal (GI) microbiotas.[5] Numerous studies have found that dietary components such as macronutrients fiber, and phytochemicals have a direct impact on the composition and metabolic activity of these communities of microbes.[6] [7] For instance, a high-sugar or high-fat diet (HFD) has been linked to dysbiosis in the two kinds of oral and gut microbiotas, which may contribute to the onset of oral diseases, GI disease and systemic health issues.[8] [9]

The complex processes by which diet affects human health are best understood by studying the interaction between our oral and gut microbiotas. The oral microbiota can affect the gut microbiota by means of mechanisms like oral microbe translocation and immune regulation.[10] The oral cavity is a portal through which microorganisms enter the digestive tract. By modulating inflammatory processes, immune system responses, and the metabolism of nutrients, the gut and the intestinal microbiota can also affect oral health.[11] [12]

Although the oral–gut microbiota connection and dietary effects on these microbial ecological systems have been the subject of numerous studies, there are still substantial knowledge gaps that need to be filled. In addition, there is a lack of understanding of the mechanisms that underpin the interaction that exists between oral and gut microbiotas. The specific pathways and signaling molecules involved in microbial translocation, immune regulation, and metabolic cross-talk still need to be elucidated

The primary objective of this review is to comprehensively explore the intricate relationship between the oral and gut microbiotas, with a specific focus on the impact of diet on these microbial ecosystems. By synthesizing existing literature and emphasizing key research findings, the review aims to shed light on how different dietary components modulate the dynamic communication between the oral and gut microbiotas. Additionally, the review seeks to elucidate the role of dysbiosis in the oral–gut axis and its potential contribution to various health conditions, including oral-related issues, GI disorders, and systemic health problems. Through this exploration, the review aspires to provide valuable insights for more precise interventions and individualized dietary approaches that promote a balanced oral–gut axis and enhance overall human health.

Methods

A bibliographic search of 78 scientific articles was carried out from PubMed Central, Web of Science, Scopus, and Google Scholar, Saudi digital library from the January 2000 till August 2023. We focused on English-language articles on microbiota, oral health, gut microbiota, dysbiosis, diet, and nutrition from the last two decades. The search strategy was created by identifying key terms and phrases related to the topics. Boolean operators were used to combine “microbiota,” “oral health,” “gut microbiota,” “dysbiosis,” “diet,” and “nutrition” in the search queries. One search query included “(microbiota OR oral microbiome OR microbial flora) AND (gut OR intestinal microbiota) AND (diet OR nutrition OR dietary components) AND (dysbiosis OR oral health OR GI diseases).” We screened the preliminary search findings' titles and abstracts to determine their relevance to the research questions and narrative review. Articles that did not meet the inclusion criteria—oral–intestinal microbiota interaction and diet and nutrition—were excluded. In order to avoid duplication, a comprehensive examination was carried out during the screening phase. After screening, the full texts of the selected articles were obtained and critically reviewed to gather relevant information and valuable insights. The reference lists of these articles were also examined for additional sources that could enhance the narrative. We systematically grouped the data from the chosen sources into thematic groupings that matched the primary research inquiries and objectives of the literature review to present a coherent and organized account. The findings were synthesized and presented in a narrative format, with the goal of offering a comprehensive overview of the subject matter, while specifically emphasizing current knowledge and health implications.

This review comprises studies that investigate both animal and human subjects.[3] [4] [13] A wide range of sample types were utilized in human studies to profile microbiota. Fecal samples were primarily employed to evaluate the composition of the gut microbiota.[2] [14] [15] Regarding oral microbiota, results obtained from a range of sample types were taken into account, encompassing oral cavity tissue samples, mucosal samples, and saliva samples.[16] [17] [18] This methodology facilitates a comprehensive analysis of the microbial communities residing in various niches. The incorporation of diverse sample types enhances the reliability and relevance of the inferences derived from the synthesis of research.

Mechanisms of Interaction

There are complex mechanisms at play in the relationship between the microbiotas of the mouth and the digestive tract, both of which affect and are affected by one another. [Fig. 1] depicts a schematic illustration of the connection between the oral and gut microbiota. The interaction between these microbial communities has been explained in various ways. These include microbial translocation, immune modulation, and metabolic cross-talk.

Fig. 1 Schematic showing the connection between the oral and gut microbiota.

Microbial Translocation

Microbes can be translocated from the oral cavity to the GI tract through a number of different mechanisms, including ingesting, aspiration, and translocation across mucosal surfaces.[19] This exchange of microorganisms has the potential to alter the makeup and function of the recipient microbiota by introducing novel taxa to the gut or oral microbiota.

Immune Modulation

The oral and GI microbiotas exert a substantial influence on the host immune system. Oral bacteria can influence the maturation and development of the gut immune system, influencing immune cell populations, cytokine production, and the immune response as a whole.[20] Immune components and mediators can impact the makeup and interaction of the oral and gut microbiota, thereby promoting immune homeostasis.

Metabolic Cross-Talk

The oral and GI microbiotas engage in metabolic interactions that can affect host physiology. Various metabolites, such as short-chain fatty acids (SCFAs) and secondary metabolites, are produced by microbial metabolism in the oral cavity.[21] These metabolites can be transported to the GI tract, where they modulate microbial composition, impact host metabolism, and influence systemic health outcomes. Some examples of specific microbial species that have been implicated in the interplay between the oral and gut microbiotas are as follows:

Porphyromonas Gingivalis

Evidence suggests that this oral pathogen promotes gut inflammation via microbial translocation and immune activation, which is linked to periodontal disease.[22] [23]

Fusobacterium Nucleatum

This oral microbe has been found in the GI tract, and it has been linked to the development of colorectal cancer due to its ability to favor inflammation and the progression of tumours.[24] [25]

Streptococcus mutans

This oral bacterium is the primary agent responsible for the development of dental caries. It has also been linked to gut dysbiosis and a variety of other negative systemic health effects, including cardiovascular disease.[18]

Bifidobacterium and Lactobacillus

The probiotic properties of these gut microbes have been the subject of extensive research, and they have shown promise in modulating oral health outcomes like lowering rates of dental caries and bacteria that cause periodontal disease.[26] [27]

Akkermansia Muciniphila

Metabolic and digestive health both improve with the presence of this gut bacterium. Recent studies have shown that it may have an effect on oral health by altering the composition of the microbes living in the mouth.[28] [29]

Clostridium Difficile

Oral colonization by this pathogenic bacterium has been linked to antibiotic-associated diarrhea and colitis, suggesting an oral–gut transmission route.[30]

The research showed that oral P. gingivalis administration caused a shift in the bacterial makeup of the ileal microbiota.[31] A separate study demonstrated that Prevotella in the tongue coating is positively associated with the presence of Prevotella in the intestines.[32] This may serve as a point of reference for the investigation of the oral and intestinal microbiota in relation to diseases. Yet another research study investigated the migration of oral microbiota to the GI tract in elderly individuals. Genomic DNA was obtained from all samples, and microbiota analysis was conducted by sequencing the bacterial 16S rRNA genes. Twenty-nine elderly subjects (mean age 80.2 ± 9.1 years) and thirty adults (mean age 35.9 ± 5.0 years) provided oral samples from subgingival plaque and tongue-coating, as well as fecal samples. The elderly group exhibited a greater degree of similarity between the microbiota found in their fecal matter and that found in their subgingival plaque, compared to the adult group. This study suggests that oral healthcare in the elderly can influence the composition of their gut microbiota, which in turn may have a positive impact on human health.[13]

By elucidating the underlying interaction mechanisms, future research may identify new therapeutic targets and recommend strategies to improve oral and gut health. Understanding how particular dietary factors affect interactions between the oral and gut microbiotas requires investigation into the impact of diet on these mechanisms.

Impact of Diet on Microbial Composition and Diversity

The oral and gut microbiotas are highly responsive to dietary patterns. In both the oral and intestinal microbiota, unique dietary variables and components have been shown to affect the diversity of microbes, community structure, and the abundance of key taxa. Several dietary factors, such as macronutrients, fiber, prebiotics, probiotics, and phytochemicals, have been the subject of extensive research in this area.[5]

Macronutrients

Carbohydrates

Carbohydrates play a crucial role as a dietary constituent, exerting an influence on the composition of diverse microbiomes within the human body.[33] The oral microbiome has been found to exhibit a higher prevalence of cariogenic bacteria, including Lactobacillus, A Actinomyces gerencseriae, A. dentails, S. mutans, C. albicans, Scardovia wiggsiae and P. acidifaciens, Capnocytophaga gingivalis, and P. gingivalis when individuals consume diets that are rich in sugars and refined carbohydrates.[34] The metabolic process of these bacteria leads to the generation of acids, which in turn causes the demineralization of tooth enamel. High-carbohydrate diets have been linked to an increase in carbohydrate-utilizing microbes, such as Prevotella and Bacteroidetes in the oral cavity and gut, respectively.[35] [36] The exclusive consumption of high-glycemic foods has the potential to elevate gingival and periodontal inflammation and bleeding. Conversely, a diet rich in complex carbohydrates, without any accompanying increase in overall energy intake, could potentially reduce the likelihood of developing gingivitis and periodontitis.[37]

Protein

On the other hand, protein-rich diets may contribute to the development of protein-degrading bacteria, such as Fusobacterium and Clostridium species in the oral cavity and Enterobacteriaceae in the gut.[5] Proteins exert a substantial influence on the composition and structure of the microbiome. The consumption of animal protein has been found to be correlated with elevated levels of insulin-like growth factor 1, which has been implicated in the development of cancer. Conversely, the intake of vegetable protein has been associated with a reduced likelihood of experiencing cardiovascular disease, diabetes, and kidney complications. The impact of proteins on the oral microbiome is significant, potentially leading to changes in its composition. Moreover, within the GI tract, proteins have the potential to exert an impact on the composition of the microbial community by serving as substrates for different groups of bacteria.[38] Alterations in protein consumption have the potential to induce modifications in the proportional representation of bacteria that possess the capability to degrade proteins within the GI tract, consequently influencing the overall composition of the gut microbiota.[37] The intricate interaction between protein sources and the microbiome highlights the significance of taking dietary choices into account in relation to the health of the microbiome.

Lipids

HFDs have been found to induce alterations in the composition and abundance of gut microbes, resulting in a reduction in microbial diversity and an elevation in the prevalence of specific microbes such as Firmicutes. The alterations observed in the gut microbiota are correlated with dietary patterns and can potentially impact one's overall health.[39] A recent study examined how a HFD affected dysbiosis, gingival blood flow, and periodontal matrix remodeling. Two experimental groups were formed: A HFD-induced dysbiosis group and a probiotic model group treated with Lactobacillus rhamnosus GG (LGG) for 12 weeks. Feces were collected before sacrifice and analyzed for SCFAs, DNA, and metagenomic sequencing. The study found that the HFD reduced Bacteroidetes, SCFA, and gingival blood flow. In contrast, Firmicutes, lipopolysaccharide -binding protein, toll-like receptor 4, pro-inflammatory cytokines (tumor necrosis factor-α, interlukin-1β, interleukin-6), matrix metalloproteinases (MMP-2 and MMP-9), and bone resorption markers (osteoprotogerin and receptor activator of nuclear factor kappa-B ligand) increased. The observed modifications suggest molecular restructuring due to inflammation, matrix degradation, and functionality changes. These changes may reduce gingiva blood flow and cause alveolar bone loss, causing periodontal disease. LGG treatment appeared to mitigate the effects of the HFD. This study shows that dietary lipids significantly affect the oral microbiome and may affect oral and systemic health.[40] The research on influence of dietary lipids on the oral microbiota is still ongoing.

Fiber

Compelling evidence from both preclinical and clinical studies has demonstrated that SCFAs like acetate, propionate, and butyrate are produced during fermentation of dietary fiber, especially indigestible plant fibers, by gut bacteria. SCFAs have been linked to anti-inflammatory and metabolic benefits, making them an important part of gut health maintenance.[41] [42] [43] Multiple studies elucidate how the ingestion of various diets, in diverse geographic regions and socioeconomic contexts, can modify microbial communities in the human GI tract.[44] [45] [46] A shared characteristic among these studies is that individuals from less developed and rural societies have a notably higher intake of dietary fiber compared to those from industrialized nations.[6] [15] Metabolic and inflammatory diseases, such as obesity and inflammatory bowel disease (IBD), are remarkably rare among individuals residing in unindustrialized nations. The study found that Papua New Guineans who followed a high-fiber diet had a significant presence of Prevotella in their microbiota, while having low levels of Faecalibacterium, Ruminococcus, Bifidobacterium, Bacteroides, Blautia, Bilophila, and Alistipes. [47] In a study conducted by Yatsunenko et al,[45] it was found that the microbiota populations of individuals from Venezuela, Malawi, and the United States showed similar results. Intestinal populations of fiber-degrading bacteria like Bacteroidetes and Firmicutes are shown to increase in response to fiber-rich diets.[48] [49] In addition, prebiotic fibers like resistant starch and oligosaccharides selectively promote the growth of probiotic bacteria like Bifidobacterium and Lactobacillus.[50] Furthermore, there were observed associations between the consumption of a plant-based diet and the presence of the microorganisms Roseburia, Eubacterium rectale, and Faecalibacterium prausnitzii,[5] along with higher overall levels of SCFAs.

Prebiotics

Prebiotics play an important role in the complex interplay of the oral and gut microbiomes, and their impact on overall health and nutrition has been well documented. Prebiotics are nondigestible compounds that feed the beneficial bacteria that reside in the GI tract. These compounds promote the growth and activity of specific beneficial microbes, resulting in a more balanced microbial environment in the oral and GI microbiotas.[51] [52] [53] Prebiotics are nondigestible compounds that favorably influence the development and function of resident beneficial bacteria. Inulin, galactooligosaccharides, and fructooligosaccharides are all kinds of oligosaccharides. Prebiotics have been shown to improve the composition of the oral and GI microbiotas by increasing the number of beneficial bacteria, especially Bifidobacterium and Lactobacillus species.[54] They can also increase the production of SCFAs, which have many positive health effects, by modulating microbial metabolism.[50] The importance of prebiotics in maintaining the balance of oral and gut microbiomes cannot be overstated. They are an essential component of the complex relationship between diet, nutrition, and the microbiome because of their ability to selectively nourish beneficial microorganisms and promote the production of health-promoting metabolites.

Probiotics

Probiotic strains like Lactobacillus and Bifidobacterium can temporarily colonize the oral and gut microbiotas and alter the composition of resident microorganisms.[55] By favoring beneficial bacteria and suppressing the growth of pathogens, probiotics may help restore microbial balances and improve oral and gut health.[56] Probiotics can have a wide range of effects, but this varies not only by strain but also by dosage and individual differences.[57] The beneficial effects of probiotics on oral health are briefly explained in [Table 1].

Table 1 Effects of probiotics on oral health and disease

Oral health issues	Effects of probiotics on oral health	References
Caries	Probiotics reduce dental caries occurrence. Milk supplemented with probiotics decreases cavitated lesions. Probiotic curds increase salivary pH and reduce Streptococcus mutans. Lactobacillus paracasei SD1 diminishes mutans prevalence	[91] [92]
Periodontitis	Probiotics prevent plaque formation, modulate salivary pH, and enhance immune responses. Inhibit production of pro-inflammatory cytokines oral sachets improve scaling outcomes. L. plantarum L-137 and probiotic lozenges benefit periodontal health	[93] [94] [95]
Halitosis	Probiotics like L. salivarius, L. reuteri, S. salivarius, and Weissella cibaria effectively treat halitosis. Chewing gum, tablets, and capsules show efficacy in reducing foul smell, gingival bleeding, and plaque	[96] [97] [98]
Oral candidiasis	Probiotics inhibit Candida growth, boost mucosal immunity, and protect the epithelial barrier. Clinical studies suggest mitigation of oral thrush symptoms, enhanced effectiveness of antifungal treatment, and preventive role	[26] [57] [99] [100]

Phytochemicals

The complex oral–gut microbiome relationship is greatly influenced by phytochemicals, bioactive compounds abundant in plant-based foods. These compounds are studied for their ability to alter mouth and stomach microbial communities. Polyphenols, phytochemicals, are found in many plant-based foods, including green tea, red wine, and many fruits and vegetables. Polyphenol-rich foods have remarkable antimicrobial properties and can finely tune oral and gut microbiota species[58]. Grapes are a good example of phytochemical benefits. Grapes contain resveratrol, which increases gut microbial diversity and metabolic function. Resveratrol's promotion of microbial diversity can help maintain a healthy gut microbiome.[59] Through their interactions with oral and gut microbiota, phytochemicals offer a compelling view of plant-based diets' potential to improve oral and gut health. In diet, nutrition, and the microbiome, phytochemicals are interesting due to their antimicrobial properties and ability to modulate specific microbial species.[60] [61]

Dysbiosis and Disease Associations

Several diseases and conditions have been linked to dysbiosis, which is defined as an imbalance or disruption in the microbial composition and function within the oral–gut axis. Growing research shows that imbalances in the microbiota of the mouth and digestive tract can have serious effects on human health.[22]

Oral Diseases

Dysbiosis has been studied extensively, and one of the areas is oral health. The oral microbiota has the capability to generate metabolites within the oral cavity, thereby exerting an influence on the progression of various oral diseases. The complex interplay between the oral microbiota and a range of oral diseases highlights the crucial significance of microbial dysbiosis in the development of these conditions.

Dental Caries

Dental caries, also referred to as dental decay or dental cavities, is a highly prevalent oral ailment that is observed on a global scale. The presence of dysbiosis within the oral microbiota is known to have a substantial impact on the onset and progression of dental caries. The microorganisms implicated in this particular biological process encompass Streptococcus mutans, Prevotella, Lactobacillus, Dialister, and Filifactor spp.[36] [62] These bacteria are recognized for their capacity to generate acids from sugars consumed in the diet, resulting in the demineralization of dental enamel. The occurrence of dysbiosis, which is frequently influenced by excessive sugar intake and inadequate oral hygiene practices, can facilitate the growth and expansion of acid-producing bacteria, thereby establishing a favorable environment for the development of dental caries.[63] A thorough understanding of the significance of microbial dysbiosis in dental caries is required in order to effectively prevent and manage this common oral ailment. The preceding information emphasizes the importance of preserving a harmonious oral microbiota through appropriate oral hygiene practices and dietary choices in order to reduce the likelihood of dental caries and improve overall oral well-being.

Periodontal Disease

Periodontal diseases, such as gingivitis and periodontitis, pose a substantial public health issue due to their chronic inflammatory nature and the resulting tissue damage occurring in the oral cavity.[21] [22] [64] The occurrence of dysbiosis within the oral microbiota is strongly linked to the initiation and advancement of periodontal diseases. Periodontitis has been associated with the involvement of particular pathogens, namely P. gingivalis, Treponema denticola, and Tannerella forsythia. These pathogens are commonly referred to as the “red complex.” These microorganisms are well-known for their capacity to facilitate the development of persistent inflammation and degradation of bodily tissues. The presence of dysbiosis within the oral microbiota has the potential to result in an excessive proliferation of pathogenic species, consequently playing a role in both the onset and severity of periodontal diseases.[65] [66] It is crucial to understand the role of these pathogens in periodontal diseases in order to develop more effective treatments and disease management strategies. This data supports the hypothesis that reestablishing a healthy microbiome can help prevent and treat a variety of oral health issues.

Oral Lichen Planus

It has been found that certain microorganisms in the oral microbiota are associated with oral lichen planus (OLP), a chronic inflammatory condition.[67] Research is still being conducted, but preliminary findings suggest that Candida species and certain strains of Streptococcus may be involved in microbial dysbiosis in OLP. According to recent research, there has been a notable increase in the levels of Porphyromonas, Fusobacterium, Leptotrichia, Lautropia, and Solobacterium in individuals OLP. Conversely, the levels of Haemophilus, Corynebacterium, Cellulosimicrobium, Campylobacter, and Streptococcus have shown a significant decrease in abundance among individuals with OLP.[68] In order to comprehend the etiology of lichen planus and investigate possible therapeutic avenues, an understanding of the microbial triggers associated with the condition is essential.

Leukoplakia

The investigation of dysbiosis in the oral microbiota has garnered attention in relation to leukoplakia, an oral lesion with precancerous potential. Research findings have indicated a potential correlation between leukoplakia and particular microorganisms such as Candida species, elevated levels of Streptococcus, and specific strains of Fusobacterium. The presence of microbial signatures in this particular condition prompts significant inquiries regarding the potential involvement of these microorganisms in its pathogenesis. While colonization with Candida albicans is frequently observed, oral leukoplakia (OLK) demonstrates a higher prevalence of Fusobacteria and lower levels of Firmicutes. The bacterial colonization patterns observed in OLK exhibit significant variability, leading to the identification of five distinct bacterial clusters. The observed clusters demonstrate the concurrent presence of Fusobacterium, Leptotrichia, and Campylobacter species, which bears a remarkable resemblance to the patterns of microbial cooccurrence observed in cases of colorectal cancers.

Oral Squamous Cell Carcinoma

The development and progression of oral squamous cell carcinoma (OSCC) are influenced by a multifaceted interaction among genetic factors, lifestyle choices, and microbial influences. Recent studies have provided evidence suggesting that specific microorganisms, namely Fusobacterium nucleatum and Pseudomonas aeruginosa, might exert influence on chronic inflammation and potentially contribute to the advancement of OSCC.[69] According to research findings, the phylum Bacteroidetes and the genera Streptococcus and Solobacterium exhibit notably elevated levels in OSCC.[70] [71] The abundance of Fusobacterium at the genus level exhibited an increase, whereas the numbers of Streptococcus, Haemophilus, Porphyromonas, and Actinomyces demonstrated a decrease in relation to the progression of cancer. The microorganisms Fusobacterium periodonticum (F. periodonticum), Parvimonas micra, P. gingivalis, Streptococcus constellatus, Haemophilus influenzae, and Filifactor alocis exhibited an association with OSCC and demonstrated a gradual increase in prevalence from stage 1 to stage 4.[16] The comprehension of microbial signals in OSCC holds significant importance in the identification and clarification of potential therapeutic targets.

Gut-Related Disorders

Several illnesses have been linked to dysbiosis in the digestive tract. Dysbiosis in the gut microbiota has been linked to gastroesophageal reflux disease (GERD), a condition that is characterized by the reflux of gastric contents into the esophagus. Symptoms of GERD may originate in the gut due to inflammation and dysfunction brought on by microbial imbalances, such as an increase in pathogenic bacteria and a decrease in beneficial bacteria.[72] [73] [74] Specific oral bacteria, such as P. gingivalis, have the ability to migrate to the GI tract, leading to significant alterations in the composition of the gut microbiota. IBD is a persistent inflammatory condition affecting the GI tract, encompassing ulcerative colitis (UC) and Crohn's disease (CD). Gut dysbiosis, which refers to the disturbed microbial community in the gut, is a characteristic feature of IBD. Gevers et al conducted an analysis and found a strong correlation between changes in the microorganisms present in the intestinal lining and the state of disease. They observed an elevated presence of Veillonellaceae, Pasteurellaceae, Enterobacteriaceae, Neisseriaceae, Gemellaceae, and Fusobacteriaceae, while the abundance of Bacteroidales, Erysipelotrichales, and Clostridiales was reduced.[75] [76] It is important to note that the enriched bacterial taxa are commonly found in the oral cavity. Likewise, the buildup of bacteria originating from the mouth is also observed in individuals diagnosed with UC. A group of children with newly diagnosed and untreated UC who had severe inflammation showed a significant rise in the number of oral bacteria, including Veillonella dispar, Aggregatibacter segnis, Campylobacter spp, Lachnospiraceae, Veillonella parvula, Haemophilus parainfluenzae, and Megasphaera spp. Therefore, bacteria originating from the mouth inadvertently establish themselves in the intestines of patients with IBD, including both CD and UC. Zhang et al conducted a study on the dynamics of the salivary microbiome during different phases of CD. They identified specific taxa and functional categories that may be associated with the development of CD. These findings suggest that these markers could potentially be used to diagnose the active disease.[17] Dysbiosis in the gut microbiota has also been linked to colorectal cancer, a major public health concern.[77] Fusobacterium species, such as F. nucleatum, are found in higher amounts in patients with colorectal cancer. The presence of a large amount of F. nucleatum is directly linked to microsatellite instability-high status and shorter survival, suggesting that the abundance of F. nucleatum is associated with poorer clinical outcomes.[78] [79] Fusobacterium nucleatum typically exists in conjunction with other organisms in the oral microbiota, including Porphyromonas spp, particularly P. gingivalis. While the majority of studies on the microbiome of colorectal cancer use fecal samples, there are also studies that examine the bacteria present in colorectal tissue specimens. These studies use quantitative polymerase chain reaction and 16S rDNA sequence analysis on 95 pairs of carcinoma and normal DNA. In these specimens, the presence of Bacteroidetes and Firmicutes was found to be reduced.[14] [24] The implications have wide-ranging effects beyond the realm of oral hygiene, as they have been associated with a variety of systemic diseases like obesity, atherosclerosis, Alzheimer's disease, rheumatoid arthritis (RA), and diabetes are among the prominent conditions that have been linked to the perturbation of the gut microbiota by these oral bacteria as illustrated in [Fig. 2].[80] [81] [82] This finding is consistent with the observed alterations in the oral microbiota profile of individuals with Alzheimer's disease, including a higher prevalence of the genera Moraxella, Leptotrichia, and Sphaerochaeta.[83] Significantly, the ability of oral microbiota to undergo translocation to other organs is recognized as an additional mechanism by which oral dysbiosis can induce systemic disease[77] [84] P. gingivalis, an oral pathogen, has been identified in the brain tissues of Alzheimer's disease patients with short-term postmortem.[85] Additionally, a variety of oral bacteria that live in harmony with their host were found in the plaques that form in the arteries of patients with coronary artery disease. This finding provides further evidence that oral bacteria may migrate to other parts of the body. Furthermore, the proliferation of the Anaeroglobus genus has been observed in the oral microbiome of individuals suffering from symptomatic atherosclerosis.[86] Peng et al conducted a comprehensive analysis of existing research data and determined that the microbial composition of the oral cavity in patients with RA is influenced by the disease. The study indicates a potential association between the oral microflora and RA.[87] Previous research has identified heat shock proteins, specifically hsp 70, from specific oral bacteria, including Prevotella nigrescens and Prevotella intermedia, in both the blood serum and synovial fluid.[88] Furthermore, the genetic material of P. gingivalis, Tannerella forsythia, and P. intermedia was detected in synovial fluid samples from patients diagnosed with RA.[89]

Fig. 2 Systemic illnesses linked to oral microbiota dysbiosis. Oral microbiota has been found to impact the development and progression of systemic diseases by triggering an inflammatory response either through oral infection or the colonization of oral microbiota in other organs or tissues within the human body. These organs and tissues include the gastrointestinal tract, the cardiovascular system, the circulatory system, the central nervous system, cancers, and joints.

The compelling evidence derived from both animal and human studies indicates that there exists a potential association between the oral–gut microbiota connection and the development of these diseases.[90] This emerging field of study is positioned to reveal innovative perspectives for subsequent inquiries and possible therapeutic interventions.

Future Directions and Research Gaps

Despite progress in understanding the oral–gut microbiota connection and diet's effects on microbial composition, several research gaps remain. To advance microbiota research and clinical practice, we must identify these gaps and propose future research.

Longitudinal Studies and Intervention Trials

Longitudinal studies that track the oral and gut microbiotas over time are required to comprehend the dynamics and permanence of microbial communities, as well as their reaction to various dietary interventions.

Characterization of Diverse Populations

The majority of microbiota research has been conducted on people from the West, constraining our knowledge of microbial diversity and function in different ethnicities, geographic regions, and cultural dietary practices. Future research should include various populations to determine the impact of genetics, lifestyle, and diet on the oral–gut microbiota relationship. This will enable the development of individualized dietary suggestions and interventions that take into account the distinct microbial profiles of various populations.

Mechanistic Studies

Mechanistic research is needed because, despite advances in linking the oral and gut microbiotas to health outcomes, the mechanisms underlying these interactions are still poorly understood. The specific mechanisms by which oral bacteria affect the gut microbiota and vice versa should be the focus of future research. Researching microbial translocation, immune modulation, metabolic crosstalk, and the effect of microbial metabolites on host physiology are all possible avenues to pursue.

Translational Challenges

Challenges arise when trying to put findings from studies of the microbiota into actual clinical practice. Reliable and comparable results across studies rely on the uniformity of methodologies, gathering samples, and data analysis protocols. The validation and incorporation of microbiota-based diagnostics and therapeutics into current clinical practices are also a time-consuming and laborious process. Recommendations for clinical applications and the efficacy of microbiota-based interventions require large-scale, multicenter studies. Addressing these gaps in knowledge and embracing new avenues for the study will help us understand the oral–gut microbiota connection and its health effects. This knowledge can enable microbiota-based diagnostics, targeted therapeutics, and personalized oral and gut health management.

Conclusion

To summarize, this literature review has explored the complex relationships between oral and gut microbiotas, revealing the significant influence of diet. The oral–intestinal axis plays a crucial role in determining overall health and disease outcomes, as shown in [Fig. 3]. This investigation emphasizes the importance of embracing a comprehensive perspective on human health that takes into account the intricate interconnections within these microbial communities.

Fig. 3 Intricate relationship between the oral and gut microbiotas and the substantial effect of diet. Symbiotic microbiota refers to microorganisms that naturally inhabit and maintain a mutually beneficial relationship with the host. Dysbiotic microbiota refers to an imbalance or disruption in the composition and function of the microbial communities.

Extending beyond academic research, the findings outlined in this review could have substantial ramifications for the control and treatment of diseases. The understanding of the oral–intestinal axis's significance presents opportunities for novel methods in diagnostics, therapeutics, and health management. The prospective advancement of microbiota-based diagnostics and personalized therapeutic interventions shows potential for improving oral and gut health. These advancements could revolutionize healthcare practices, providing tailored solutions based on individual microbial profiles.

In conclusion, this review not only summarizes the current state of knowledge, but also emphasizes the urgency of ongoing research. The future holds promise for a paradigm shift in healthcare, with microbiota-based approaches playing a critical role in improving human health and managing a wide range of diseases.

Conflict of Interest

None declared.

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Article published online:
26 September 2024