Mouth and gut microbes talk to each other - here’s why it matters for disease

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Aug 4 2025

A landmark review uncovers how your mouth’s microbes shape gut health, immunity, and chronic disease, making oral care a frontline strategy for whole-body wellbeing.

Review: The Oral–Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction. Image Credit: Shutterstock

In a recent study in the journal Nutrients, researchers collated and synthesized almost 250 peer-reviewed publications investigating the "oral-gut axis," a complex, bidirectional communication network linking the gut microbiome and its much less studied oral counterpart (oral microbiome).

Review findings underscore that oral pathogens can migrate to the gut, triggering dysbiosis and contributing to systemic diseases like inflammatory bowel disease (IBD), colorectal cancer, and cardiovascular diseases (CVDs). This crosstalk is mediated by direct bacterial translocation and by several microbial metabolites, including Trimethylamine N-oxide (TMAO) and specific lipopolysaccharides (LPS), as well as other metabolites such as short-chain fatty acids (SCFAs), bile acids, and indole derivatives.

The review also highlights the importance of beneficial commensal microbes and dietary factors, such as fiber, polyphenols, and probiotics, in maintaining a healthy oral-gut axis. Maintaining oral health is a critical, yet often forgotten, component of overall systemic wellbeing.

Why the mouth matters 

The extensively studied gut microbiome has been hailed for over a decade as a master regulator of human health, influencing everything from immune function and metabolism to neurology and mood. However, science has largely ignored that the digestive tract that culminates in the gut begins in the mouth.

Notably, a handful of studies investigating gut microbial composition report that the oral cavity hosts its own distinct and complex microbial community of over 700 microbial species. Even when studied, the oral microbiome has been studied in isolation and focused more on preventing gut disease and cavities than on digestion and immunity.

Recent research suggests the existence of bidirectional dialogue between the oral and gut microflora, with potentially profound implications for holistic wellbeing.

Moreover, disruptions in either microbiome, especially at different life stages, such as infancy, aging, or during chronic disease, can affect the other, emphasizing a lifespan perspective in oral-gut interactions.

Four routes of communication

The present narrative review synthesizes the steadily growing body of evidence investigating the "oral-gut axis," aiming to elucidate the mechanisms via which these distinct microbial communities interact and how these interactions influence human health.

It covers almost 250 studies across microbiology, gastroenterology, and systemic medicine, focusing on literature describing any of the three primary communication pathways that link the oral and gut microbiomes: the enteral route, which is the direct transfer of microbes via swallowing; the hematogenous route, which is the spread of microbes through the bloodstream; and the metabolite-mediated route, which involves the systemic effects of chemical compounds produced by both microbiomes.

In addition, the review describes a fourth route, the fecal–oral pathway, whereby gut microbes can reach the mouth, especially in settings of poor hygiene or sanitation, further supporting a bidirectional model of communication.

The review then thoroughly examines and synthesizes evidence for each pathway, thereby presenting a cohesive picture of how oral dysbiosis (an imbalance of microbes in the mouth) can directly influence gut health and trigger systemic disease, while also highlighting potential protective strategies including diet, prebiotics, and probiotics.

The enteral route 

The extensive body of literature reviewed highlights that the connection between the mouth and gut is dynamic, multifaceted, and far more interconnected than commonly believed.

Humans swallow 1 to 1.5 litres of saliva daily, serving as a conduit for billions of oral bacteria. While most are killed by stomach acid, some resilient pathogens can survive, particularly in individuals with weakened defenses, such as those using proton-pump inhibitors.

Pathobionts like Porphyromonas gingivalis and Fusobacterium nucleatum, both key players in periodontal (gum) disease, have been demonstrated to colonize the gut and are strongly implicated in driving inflammation-associated chronic conditions like inflammatory bowel disease (IBD).

The review notes that certain oral microbes, such as Prevotella species, can also be detected in stool under normal physiological conditions. Alarmingly, these oral microbes have been associated with promoting the growth of colorectal tumors.

The hematogenous route 

While substantially harder to invade, the bloodstream presents a far more sinister route of entry for oral bacteria into systemic circulation than the digestive tract. Poor oral health, especially periodontitis, creates inflamed, ulcerated gums that serve as a direct entry point for oral bacteria to invade the circulatory system.

This "oral bacteremia" allows pathogens to travel to distant organs, including the gut, where they can disrupt the intestinal barrier, causing the "leaky gut" syndrome, and trigger systemic inflammation. This may, in turn, trigger a cascade where pathogenic gut bacteria can then use this leaky gut to invade the bloodstream, giving rise to an entirely independent set of infections.

Animal and human studies suggest that bloodstream spread may be particularly important for some pathogens, such as Fusobacterium nucleatum, which are linked to both gut inflammation and colorectal cancer.

Oral bacteria in circulation may also exacerbate systemic inflammation, metabolic disorders, and even affect the gut microbiota composition.

Metabolite-mediated communication 

Metabolite-mediated interactions are the most complex of oral-gut interactions. Both cohorts, the oral and gut microbiomes, produce a diverse and largely independent array of bioactive compounds. Trimethylamine N-oxide (TMAO), a metabolite strongly linked to atherosclerosis, is possibly the best studied.

Notably, TMAO is produced in a two-step process wherein gut bacteria first convert dietary nutrients like choline and carnitine from red meat and eggs into trimethylamine (TMA), which the liver enzyme flavin-containing monooxygenase 3 (FMO3) then converts to TMAO.

Alarmingly, oral pathogens like P. gingivalis can exacerbate this process by increasing systemic inflammation, which in turn stimulates FMO3 expression and raises circulating TMAO levels, in turn severely increasing atherosclerosis risk.

The review further details that other metabolites, including short-chain fatty acids (SCFAs), indole and its derivatives, and altered bile acids, play critical roles in regulating inflammation, immune responses, gut barrier integrity, and systemic disease risk. For example, butyrate, a SCFA produced in the gut, can have both anti-inflammatory and metabolic effects. Indole derivatives may protect the gut barrier and modulate immune balance.

The balance of these metabolites is affected by both oral and gut microbiome health, as well as by dietary patterns.

The fecal-oral pathway 

The review highlights the significance of the fecal–oral pathway, especially in poor sanitation or immunocompromised states. Microbes from the gut can reach the oral cavity via contaminated food, water, or direct contact, affecting both oral and gut health.

This pathway is also relevant to the spread of certain viruses and gastrointestinal diseases.

Integrating oral and gut health 

The present review highlights the strong interconnection between oral and gut microbiomes and the importance of increasing research focused on disease and digestion on oral bacteria.

Our oral and gut microbiomes are not isolated ecosystems but are deeply interconnected parts of a larger whole. The health of our mouth directly influences the health of our gut, and vice versa, with profound implications for systemic health and clinical intervention.

The review emphasizes that dietary patterns, including high intake of dietary fiber, polyphenols, omega-3 fatty acids, prebiotics, and probiotics, can support both oral and gut microbial balance, while poor diet, excessive sugars, and alcohol can disrupt it. Preventive strategies should thus target both oral and gut health across the lifespan.

The evidence is growing, but many of the detailed mechanisms remain under investigation, highlighting the need for continued multidisciplinary research.