The oral–gut microbiota axis: the harbinger of autoimmue diseases

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The oral–gut microbiota axis: the harbinger of autoimmue diseases

Microbiome in human gastrointestinal tract (Photo: Canva)

Wed. 23 August 2023


In recent decades, we have recognized the vital role of microbiota in health and disease. The human gut and oral microbiota, the body’s largest microbial communities, are closely connected due to the mouth’s position as the start of the digestive system. Compelling new evidence reveals complex links between these two microbiota. This interaction could significantly impact the development of systemic diseases including autoimmune diseases and certain cancers.

Autoimmune diseases occur when the immune system loses the ability to differentiate between its cells as well as foreign invaders and mistakenly attacks healthy cells. So far, more than eighty autoimmune diseases have been identified, affecting various parts of the human body [1].

Furthermore, they are characterized by an immune response to self–antigens such as autoantibody-producing B cells, autoreactive T cells, and proinflammatory cytokines [1].

Recent studies reveal that oral and gut microbiota dysbiosis have a pivotal role in the initiation and progression of a broad spectrum of autoimmune diseases [1,2]. The microbiota dysbiosis disrupts the homeostasis between the host and commensal, accompanied by abnormal immune response leading to autoimmune diseases. The oral cavity is anatomically connected with the gastrointestinal tract (GIT), which harbors the largest and most diverse microbiota. There is approximately 45% similarity between the fecal and oral microbiota suggesting ectopic colonization of oral bacteria in GIT, by escaping the inhibition of gastric acid[1].

Figure 1. The three routes through which oral microbial flora influences gut microbiota. [3]

The three routes through which oral microbiota affects the gut microbiota are enteral, hematogenous, and immune cell migration routes. Still, there is controversy about whether oral microbiota can colonize the gut through the enteral route [3]. Recent research suggested that there was no confirmation of the colonization of oral bacteria in the distal gut of healthy adults. In contrast, some researchers indicated that at least one in three oral microbiotas can sustain in a healthy adult gut. For example, mouth–to–gut transmission was higher in rheumatoid arthritis patients.

Generally, dental procedures and periodontitis permit the spread of salivary microbiome, oral bacteria, and periodontal pathogens such as P. gingivalis, F. nucleatum, and A. actinomycetecomitans into the bloodstream. In the immune cell migration route, intracellular oral bacteria can exist within the immune cells such as dendritic cells and macrophages, thus facilitating easy dissemination from oral to gut mucosa. Additionally, the immune cells acquired from the oral draining lymph nodes can spread to the gut and the other lymphoid tissues. For example, oral pathobiont-reactive T helper 17 (Th17) cells, after activating with gut tropism, migrate to the inflamed gut [3] (Figure 1).

The interplay between oral-gut axis and autoimmune diseases:
The role of the oral–gut axis has been recently proposed in various autoimmune diseases. The major trigger mechanisms for the occurrence of autoimmune diseases are microbial translocation, molecular mimicry, and autoantigen overproduction[1].

The following autoimmune diseases are caused by oral–gut microbiota dysbiosis:

Rheumatoid Arthritis (RA) is a chronic progressive autoimmune disease characterized by synovial inflammation and gradual degradation of articular cartilage and bone. Autoantibodies to citrullinated proteins are one of the diagnostic criteria for RA. Citrullinated proteins are developed from posttranslational arginine modification and catalyzed by peptidyl arginine deiminases (PADs). The oral bacterium P. gingivalis is responsible for protein citrullination which further increases anti-citrullinated peptide antibodies (ACPAs). In RA patients, Anti-Pg-LPS IgG antibody levels were inversely associated with the patient’s disease activity; the serum LPS-binding protein levels were linked with disease biomarker concentrations. Thus, these findings indicated that certain proteins from oral and gut microbiota can affect disease activity in RA patients [3].

Inflammatory Bowel Disease (IBD) is a group of chronic relapsing inflammatory conditions of the GIT, which comprises two clinical types–ulcerative colitis (UC) and Crohn’s disease (CD). The main etiological causes involved in IBD progression are environmental and genetic factors. Oral microbiota contains an abundance of Enterobacteriaceae as compared with other mucosal sites. Klebsiella, an oral Enterobacteriaceae species, can ectopically colonize and sustain in the colon and cecum and thus induce gut inflammation in a genetically susceptible patient. Additionally, they also promote T helper 1 (Th1) cells during gut colonization [3].

Type 1 Diabetes Mellitus (T1DM) is characterized by insufficient secretion of insulin by the pancreas. Recent data stated that oral microbiota can induce gut dysbiosis and gradual insulin resistance. The main mechanisms for increased insulin resistance are gut dysbiosis, increased gut permeability, systemic inflammation, and metabolic derangement. Another study reported that Turibacter, a butyrate-producing bacterial population was reduced in the gut microbiota after oral gavage of P.gingivalis [3].

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that affects the connective tissue of multiple organs resulting in tissue damage and extensive inflammation. Primary Sjogren Syndrome (pSS) is an autoimmune condition caused by lymphocytic infiltration of lacrimal and salivary glands, resulting in dry eyes and mouth. Moreover, pSS and SLE share common epidemiological, clinical, pathogenic, and etiological features. Lower diversity in gut microbiota composition was observed in pSS and SLE patients while a reduced Firmicutes/Bacteroidetes ratio was present in SLE patients. However, a diversity of microbiota composition was observed in SLE and pSS patients. A study revealed that SLE is linked with increased alpha diversity in both buccal swabs and oral washings than in pSS patients [4].


Recent evidence suggests that the oral-gut microbiota axis plays a pivotal role in the pathogenesis of several autoimmune diseases such as RA, IBD, T1DM, SLE, and pSS. Moreover, the oral microbiota can influence the gut microbial population through enteral, hematogenous, and immune cell migration routes. The multifactorial causative pathways utilized by oral–gut microbiota dysbiosis for initiating autoimmune diseases are microbial translocation, molecular mimicry, and autoantigen overproduction. Hence, more research is needed to validate these findings and explore the efficacy of oral and gut microbiota-based targeted therapies for the treatment of autoimmune diseases.


1. Huang X, Huang X, Huang Y, Zheng J, Lu Y, Mai Z, Zhao X, Cui L, Huang S. The oral microbiome in autoimmune diseases: friend or foe? Journal of Translational Medicine 2023; 21:211.

2. Belvoncikova, P; Maronek ,M; Gardik ,R. Gut Dysbiosis and Fecal Microbiota Transplantation in Autoimmune Diseases. Int. J. Mol. Sci. 2022; 23, 10729.

3. Tan X, Wang Y, Gong T. The interplay between oral microbiota, gut microbiota and systemic diseases. Journal of Oral Microbiology 2023; 15: 2213112.

4. Taco A. van der Meulena, Hermie J.M. Harmsenb, Arnau Vich Vilac, Alexander Kurilshikovd, Silvia C. Lieferse , Alexandra Zhernakovad , Jingyuan Fud , Cisca Wijmengad , Rinse K. Weersmac , Karina de Leeuwe , Hendrika Bootsmae, Fred K.L. Spijkerveta , Arjan Vissinka , Frans G.M. Kroesee. Shared gut, but distinct oral microbiota composition in primary Sjögren's syndrome and systemic lupus erythematosus. Journal of Autoimmunity 2019; 97:77–8.

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