Salivary Klebsiella species can inflame the gut

Last Updated: 2017-10-26

By Will Boggs MD

NEW YORK (Reuters Health) - Intestinal colonization by Klebsiella species isolated from saliva drives T helper 1 (TH1) cell induction and inflammation in the gut, researchers report.

"Our results suggest the existence of a sub-type of inflammatory bowel disease (IBD), in which ectopic colonization of oral-derived bacteria such as Klebsiella in the intestine might causally relate to aberrant activation of the immune system," Dr. Kenya Honda from Keio University School of Medicine, Tokyo, Japan, told Reuters Health by email. "Our findings could provide a therapeutic strategy to correct IBD and other disease conditions by targeting oral-derived bacteria, particularly Klebsiella species, using new drugs, such as very narrow-spectrum antibiotics or lytic phages which specifically kill Klebsiella."

Increased levels of microbes of oral origin are present in the gut microbiota of patients with IBD, HIV infection, liver cirrhosis, and colon cancer.

Dr. Honda and colleagues searched the human oral microbiota for bacterial strains showing strong immune-stimulatory activities upon intestinal colonization. They reported their results online, October 20, in Science.

Among eight strains from diverse genera, only the multiple antibiotic-resistant Klebsiella pneumoniae isolate Kp-2H7 significantly induced TH1 cells in mice, whereas a mixture of the remaining seven strains failed to do so.

"To me, the most surprising finding was that despite the complexity of the microbiota in the oral cavity and the gut, only one bacterial species, Klebsiella, was identified as being responsible for the induction of intestinal TH1 cells," Dr. Honda said.

Colonization of intestine with this K. pneumoniae isolate did not induce any inflammatory changes in the intestine of wild-type mice, despite induction of TH1 cells. In contrast, Kp-2H7 more potently induced TH1 cells and caused severe inflammation in the proximal colon of colitis-prone IL10(-/-) mice.

Different human, mouse, and environmental K. pneumoniae strains showed considerable variability in their ability to elicit colonic TH1-cell induction. Sequence typing identified 61 groups of genes positively correlated with TH1 induction ability - genes that have previously reported to be enriched in the fecal microbiome of patients with inflammatory diseases and that have been suggested to have immunomodulatory effects.

"Our data suggest that the oral cavity may serve as a reservoir for Klebsiella pathobionts," Dr. Honda said. "Klebsiella may exist in the oral cavity of even healthy individuals. Klebsiella spp. are innocuous in the oral cavity, but proinflammatory in the intestine (depending on the host genotype) and very inflammatory in the lung (irrespective of host genotypes)."

"Klebsiella strains that were isolated in our study as strong TH1-cell inducers were resistant to several antibiotics, and treatment with antibiotics allowed their colonization in the intestine of otherwise normal mice," he explained. "Therefore, our findings are not confined to the context of inflammation, but can be extended to the context of multidrug-resistant bacteria."

"Indeed, we are now trying to identify members of the normal gut microbiota that can provide colonization resistance against Klebsiella species," Dr. Honda said. "If we could identify such beneficial bacteria, we could use them to treat patients infected with multidrug-resistant bacteria and also patients with chronic intestinal inflammation."

Dr. Purmina S. Kumar from The Ohio State University, in Columbus, who recently reviewed the role of the oral microbiome in systemic disease, told Reuters Health by email, "The oral microbiome has been implicated in the etiopathogenesis of several systemic diseases. This is another such example. The results should always be interpreted with some caution, since cross talk between the host and bacteria is highly species-specific, and results from germ-free mice cannot be directly extrapolated to humans."

"The oral cavity harbors Klebsiella as a very minor constituent of the oral microbiome," she said. "It is interesting that this oral source can cause so much dysregulation of the mucosal system in susceptible individuals."

Dr. Caroline Attardo Genco from Tufts University School of Medicine, in Boston, who also has investigated immune dysregulation mediated by the oral microbiome, told Reuters Health by email, "Numerous studies in mouse models and humans (including from our group) have demonstrated that dysbiosis of the oral microbiome is associated with inflammatory diseases both locally and systemically. Our group has also demonstrated that oral bacteria can survive and disseminate from the oral cavity in dendritic cells to sites distant from infection where they induce a chronic inflammatory response."

"Treatment of common infections with antibiotics allows for antibiotic-resistant, proinflammatory oral bacteria to colonize the gut and promote disease," she said. "These results lend further support to previous studies suggesting that probiotics or fermented foods may provide benefit to patients that have been given antibiotics. Importantly, they also support the body of literature on systemic inflammatory consequences associated with dysbiosis of the oral microbiome."

SOURCE: http://bit.ly/2z5xkj2

Science 2017.