Bottoms Up! How can gut microbiome research benefit periodontitis patients?

A key concept in studies of the human microbiome is the importance of host site-specificity to sustain specific microbial consortia. This applies to both gastrointestinal and oral niches, where the saturation capabilities of the juxtaposed microbial communities that we host determine health or disease. The gut microbiome is relatively unstable and adversely impacted by environmental stressors—including pro-inflammatory diets, psychological stress, and systemic inflammation—that can induce leakiness in the gut lining. Dysbiosis emerges and leads to altered and destructive immune-inflammatory responses that cause mucosal ulceration and morbidity.

By contrast, the oral microbiome is relatively stable once the permanent teeth erupt. Periodontal dysbiosis can be associated with increased microbial diversity—exactly the opposite of IBD—and plaque biofilm disruption can reverse that dysbiosis.

The so-called “gum-gut axis” is underpinned by evidence for oral to gastrointestinal niche transmission of certain oral bacteria in IBD, including Aggregatibacter, Campylobacter, Neisseria, Enterobectaria, Fusobacterium, Peptostreptococcus, Staphylococcus, and Streptococcus species. Indeed, the latter four organisms have also been identified in IBD biopsies.

Oral-gut transmission appears to be via several routes including blood, saliva (where mucins protect bacteria from stomach acid), keratinocytes, and immune cells. Oral pathogens such as F.nucleatum can evade immune defences, remain viable inside immune cells—including lymphocytes, macrophages, and neutrophils (Trojan horse concept)—and travel in the vasculature to the gut. Moreover, F.nucleatum, K.pneumoniae, and C.consisus can invade intestinal epithelial cells and induce cytokine production (IL-8, IL-1β, TNFα) and downstream inflammation. C.consisus also produces a toxin that disrupts tight cell junctions in the gut lining—thus further increasing gut mucosal permeability—by disrupting the intestinal barrier.

Interestingly, oral pathogens in the mouth can prime pro-inflammatory TH-17 immune cells during periodontitis, which travel to the gut via the vasculature. Here the same gut-tropic pathobionts reach the colon via the mechanisms mentioned above and activate the already primed pro-inflammatory TH-17 and TH-1-cells to cause colitis. There are therefore a series of complex pathophysiological processes through which periodontal pathogens and the associated immune responses to them seem capable of triggering and/or exacerbating IBD.

The plasticity of the gut microbiome lends itself to gut microbiome manipulation through techniques such as faecal microbiota transplantation (FMT). Clinical results for the use of FMT in C.difficile infections has proven to be lifesaving, and emerging evidence also supports benefit in UC. Microbiome manipulation is more challenging in the oral cavity because of the stability of the oral microbiome, and probiotic approaches have met with limited success. However, lessons can be learned from FMT in managing IBD and may inform novel strategies for oral microbiota transplantation (OMT) in the future.