Scientists reveal a surprising link between depression and microbes in your mouth

A new study published in the journal BMC Oral Health has uncovered a relationship between the diversity of bacteria in the mouth and symptoms of depression. Drawing from data on more than 15,000 adults in the United States, researchers found that people with lower oral microbiome diversity were more likely to experience depressive symptoms. This association was especially notable in men and non-Hispanic White individuals. The findings suggest that the oral microbiome might play a previously underappreciated role in mental health.

The human body is home to trillions of microorganisms—bacteria, fungi, viruses—that collectively make up what scientists call the microbiome. While much attention has been given to the gut microbiome’s influence on mood and behavior, the oral microbiome has received less focus.

The mouth is the gateway to the digestive system and hosts the second-largest microbial community in the body. These microbes are essential for maintaining balance in the immune system, helping prevent disease, and managing inflammation. Because of the oral microbiome’s importance in health and its interactions with the rest of the body, the researchers wanted to explore whether it might also relate to mental health, particularly depression.

To investigate this, the researchers used data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey conducted by the U.S. Centers for Disease Control and Prevention. They analyzed data collected between 2009 and 2012, focusing on 15,018 adults who had both oral microbiome and mental health data available. The participants had an average age of about 42 years and were racially and ethnically diverse.

To measure depressive symptoms, the researchers used a standard tool known as the Patient Health Questionnaire-9, or PHQ-9. This questionnaire asks participants how often they have experienced symptoms such as low mood, fatigue, or difficulty concentrating over the past two weeks. A score of 10 or higher is typically considered indicative of depression.

To assess oral microbiome diversity, participants provided oral rinse samples, which were then analyzed using a genetic technique that identifies bacterial types based on their DNA sequences. The researchers calculated two main types of diversity. Alpha diversity measures the richness and evenness of bacteria within a single person’s mouth. Beta diversity measures how similar or different one person’s oral microbiome is from another’s.

The study found a strong inverse association between alpha diversity and depression. In other words, people with a greater variety of bacterial species in their mouths were less likely to show signs of depression. This association remained even after adjusting for other factors that might influence both depression and oral microbiota, such as age, gender, race, smoking status, alcohol use, sleep problems, and physical health conditions like diabetes and hypertension.

Interestingly, the researchers also discovered a nonlinear relationship between microbiome diversity and depression. Specifically, increases in bacterial diversity were linked to a reduction in depression scores—but only up to a point. After reaching a certain threshold, additional increases in diversity were no longer associated with better mental health. This finding suggests there may be a “sweet spot” in oral microbial richness that supports mental well-being.

In addition to within-person diversity, the researchers also examined between-person variation in oral microbiomes. They found that people with depression had significantly different microbial communities compared to those without depression. These group-level differences were visualized using statistical techniques that cluster individuals based on the similarity of their microbiome profiles.

The relationship between depression and oral microbiome diversity was also shaped by certain behaviors and demographic characteristics. For instance, the negative association between bacterial diversity and depression was stronger among men and non-Hispanic White participants. Smoking, excessive alcohol consumption, and recent oral treatment—such as deep cleaning for gum disease—also affected the strength of the relationship. These findings suggest that lifestyle and environmental factors may interact with microbial diversity in shaping mental health outcomes.

The study adds to a growing body of evidence linking microbial ecosystems in the human body to mental health. While gut bacteria have long been a focus of microbiome research, the oral microbiome is now emerging as an important player in its own right.

Several potential mechanisms could explain the observed connection. Oral bacteria may affect mental health by triggering inflammation or interacting with the immune system. Some species can travel to the gut and reshape its microbial landscape, which is known to influence brain chemistry and stress responses. Other bacteria may produce metabolites that impact neurotransmitter systems involved in mood regulation.

Another possibility is that the link runs in the other direction. People with depression may engage in behaviors—such as smoking, drinking, poor diet, or inadequate oral hygiene—that disrupt the balance of bacteria in the mouth. Depression is also associated with physical changes, like increased inflammation and altered immune function, which could affect the composition of the oral microbiome. Medications used to treat depression may also have effects, especially those that cause dry mouth, which can shift the oral environment and promote the growth of certain bacteria.

The researchers acknowledge several limitations to their study. Because the data were collected at a single point in time, it is not possible to say whether changes in oral microbiota lead to depression or vice versa. Longitudinal studies, which follow people over time, will be necessary to untangle cause from effect. The study also relied on self-report measures of depression symptoms rather than clinical diagnoses, and it could not account for all possible confounding factors. Additionally, while genetic sequencing identified broad patterns in bacterial diversity, it did not examine specific species or their functional roles.

Despite these limitations, the study offers a valuable contribution to research on the microbiome and mental health. It is one of the first large-scale analyses to link oral microbiome diversity with depression in the general population. The results suggest that the mouth may be an important, and previously overlooked, frontier in understanding mental health.

“Having a better understanding of the relationship between the oral microbiome and depression could not only help us learn about the mechanisms underlying depression, but could contribute to the development of new biomarkers or treatments for mood disorders,” said Bei Wu, a vice dean for research at NYU Rory Meyers College of Nursing and the senior author of the study

Wu also emphasized that this work is part of a broader effort to examine how the oral microbiome might affect other aspects of mental health, including cognitive decline and the risk of developing dementia. Future research will need to explore how different bacterial species interact with human biology, how lifestyle factors shape the oral microbiome, and whether interventions targeting oral health—such as improved hygiene, dietary changes, or probiotics—can support better mental health.

The study, “Relationship between depression and oral microbiome diversity: analysis of NHANES data (2009–2012),” was authored by Xichenhui Qiu, Ting Xu, Yiqing Huang, Changning Wei, Lina Wang, and Bei Wu.