Oral Bacteria and Bowel Diseases Mini Review

Masahiro Yoneda^1*, Nao Suzuki², Hiromitsu Morita¹ and Takao Hirofuji¹

¹Section of General Dentistry, Department of General Dentistry, Fukuoka Dental College, 2-15-1, Tamura, Sawara-ku, Fukuoka, 814-0193, Japan

²Section of Oral Public Health, Department of Preventive and Public Health, Fukuoka Dental College, 2-15-1, Tamura, Sawara-ku, Fukuoka, 814-0193, Japan

Corresponding Author:

Dr. Masahiro Yoneda
Section of General Dentistry, Department of General Dentistry
Fukuoka Dental College, 2-15-1,Tamura, Sawara-ku
Fukuoka, 814-0193, Japan
Tel: 81-90-8626-9149
E-mail: Yoneda@college.fdcnet.ac.jp

Received Date: March 11, 2016; Accepted Date: March 21, 2016; Published Date: March 28, 2016

Citation: Yoneda M, Suzuki N, Morita H, Hirofuji T (2016) Oral Bacteria and Bowel Diseases – Mini Review. J Gastrointest Dig Syst 6:404. doi: 10.4172/2161-069X.1000404

Copyright: © 2016 Yoneda M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Gastrointestinal & Digestive System

Abstract

Oral bacteria are considered to be associated with several systemic diseases. Recently, their association with inflammatory bowel disease (Crohn's disease and ulcerative colitis) and colorectal carcinoma has attracted much attention. In this mini-review, the association of oral bacteria with these diseases is briefly summarized. Fusobacterium nucleatum is known as a periodontopathic bacterium, and it is also associated with inflammatory bowel disease and colorectal carcinoma. Campylobacter concisus, which is found at the site of periodontitis, is associated with inflammatory bowel disease. Streptococcus mutans is a famous cariogenic bacterium, but a highlyvirulent strain of this bacterium is also associated with inflammatory bowel disease. In this way, both periodontopathic bacteria and cariogenic bacteria are associated with bowel diseases. Further epidemiological studies are necessary to reveal the cause and effect relationship between oral bacterial and bowel diseases.

Keywords

Oral bacteria; Inflammatory bowel diseases; Colorectal carcinoma

Introduction

Oral bacteria are considered to be associated with several systemic diseases such as atherosclerotic disease, adverse pregnancy outcomes, rheumatoid arthritis, and respiratory tract infections [1].

Recently, the association of oral bacteria with inflammatory bowel disease (IBD) and colorectal cancer (CRC) has attracted much attention. IBDs, which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing idiopathic inflammatory diseases of the gastrointestinal tract [2]. IBD is thought to be associated with both environmental and bacterial factors. Epidemiological studies suggested that environmental factors play an important role in the increased incidence of IBD. On the other hand, colitis did not occur in germ-free animal models of IBD, and intestinal inflammation in patients with CD was resolved after faecal stream diversion [3,4].

In this mini-review, the association of oral bacteria and these diseases will be briefly summarized (Table 1).

Table 1: Oral bacteria and bowel diseases; important findings in literature review. IBD: Inflammatory bowel disease; CRC: Colorectral carcinoma.

Fusobacterium nucleatum

Fusobacterium nucleatum , which is a Gram-negative fusiform bacterium, is known as one of the most important periodontopathogens [5]. It is commonly detected at the site of periodontitis. In animal experiments, F. nucleatum shows synergistic virulence in mixed infections. When F. nucleatum and Porphyromonas gingivalis , another important periodontopathogen, were simultaneously injected to mice, larger abscesses were formed compared to mice mono-injected with each bacterium [6]. F. nucleatum coaggregates with several kinds of bacteria [7], and it contributes to biofilm formation. F. nucleatum has an outer membrane protein RadD, which is associated with coaggregation [8]. Han et al. identified an adhesion FadA that is unique to oral Fusobacteria [9]. FadA may be associated with colonization in the periodontal environment and is considered to be associated with invasion [10] and systemic dissemination [9].

F. nucleatum and IBD

Verna et al. reported that F. nucleatum septicemia in UC patients is associated with portal vein thrombosis [11]. F. nucleatum is a heterogeneous oral pathogen, and it also resides in the human gut mucosa. In the inflamed biopsy tissue from IBD patients, more invasive F. nucleatum strains are found [12]. Dharmani reported that highly invasive F. nucleatum strains stimulated MUC2 mucin and TNFαproduction [13]. McGuire et al. compared the genes between actively-invading and passively-invading Fusobacteria [14]: Active invaders had much larger genomes and encoded FadA-related adhesins containing a MORN2 domain.

F. nucleatum and colorectal carcinoma

Two reports on F. nucleatum and CRC were reported in 2012 by different authors in the same journal. Kostic reported the association of F. nucleatum with CRC [15], and Castellarin reported the positive association with lymph node metastasis [16]. Kostic et al. examined the effect of F. nucleatum on tumorigenesis by using a mouse model [17]. This bacterium increased tumor multiplicity and selectively recruited tumor-infiltrating myeloid cells. FadA is a unique adhesin of F. nucleatum , and the effect of the protein on carcinogenesis was examined. Rubinstein et al. demonstrated that F. nucleatum adhered to, invaded and induced oncogenic and inflammatory responses through FadA [18]. They also reported that FadA bound to E-cadherin and activated α-catenin signaling. F. nucleatum coaggregates with several microorganisms, which contributes to the progression of periodontitis [18].

In colorectal carcinoma, F. nucleatum is found to co-reside with other gram negative bacteria, such as Campylobacter [19]. Fukugaiti et al. reported that F. nucleatum and Clostridium difficile are detected in CRC patients [20].

F. nucleatum is also known to associate with colorectal adenomas [21]. Flangan et al. reported that F. nucleatum is associated with the progression from adenomas to CRC and suggested that detection of F. nucleatum may be useful as a diagnostic and prognostic determinant in CRC patients [22]. As for prognosis, F. nucleatum is reported to be associated with the worse clinical outcome of CRC [23]. The mechanism of CRC progression by F. nucleatum is not fully understood, but Nosho et al. reported the effect of this bacterium on T cell immunity [24].

Campylobacter concisus

Campylobacter concisus is a Gram-negative, highly fastidious, spiral, and microaerophilic bacterium [25]. C. concisus has been isolated from human gingiva and is linked with periodontal lesions, including gingivitis and periodontitis [26]. Aspartate aminotransferase (AST) is markedly elevated in gingival crevicular fluid from sites with severe gingival inflammation and progressive attachment loss, and C. concisus is often isolated from AST positive sites [27].

Campylobacter concisus and IBD

Campylobacter species, such as C. jejuni , have been recognized as important pathogens of bowel diseases [28]. Zhang et al. demonstrated that a significantly higher presence of C. concisus and significantly higher levels of IgG antibodies specific to C. concisus are present in children with CD than in controls [29], and this bacterium is now recognized as an emerging pathogen of the human gastrointestinal tract. They also detected C. concisus from the saliva of healthy individuals and IBD patients [30]. They suggested that an individual may harbor multiple C. concisus strains in the oral cavity and that some oral C. concisus strains may colonize the lower gastrointestinal tract and be involved in IBD. Ismail et al. reported that patients with IBD were colonized with specific oral C. concisus strains, which underwent natural recombination and obtained invasiveness [31].

The virulence factors of C. concisus were further investigated, and the association of immunoreactive proteins [32] and zonula occludens toxin [33,34] with IBD was reported. Survival of C. concisus in host cells and tissues were also investigated. Autophagy usually contributes to the clearance of intracellular organisms, which is true for C. concisus . However, some strains of C. concisus were found to utilize autophagy for intracellular survival [35]. Ma et al. reported that increased gastric pH and reduced intestinal bile may be beneficial for C. concisus to colonize the intestine [36]. Recently, the genes of C. concisus are being investigated. Mahendran et al. reported the genetic relatedness and population structure of oral and enteric C. concisus species [37]. The relationship between oral and enteric strains of C. concisus will be investigated in the future.

Streptococcus mutans

S. mutans is a Gram-positive oral bacterium. The bacterium metabolizes different kinds of carbohydrates, and creates an acidic environment, which is associated with tooth decay. Streptococci are also known as the cause of infectious endocarditis [38]. Recently, a highly-virulent strain of S. mutans was reported to be associated with hemorrhagic damage in the murine brain [39], and this bacterium attracts much attention in the field of general medicine.

Streptococci and bowel diseases

Sundh et al. examined the microbial features of saliva and reported the association of dental caries and Crohn’s disease [40,41]. Among the oral bacteria, S. mutans was found to be most associated with Crohn’s disease [42]. Kojima et al investigated the effect of a highly-virulent strain of S. mutans on dextran sodium sulfate-induced mouse colitis [43]. The specific strain of S. mutans , which produced a collagenbinding protein, aggravated colitis. They reported that this highlyvirulent strain of S. mutans was also associated with human IBD. The relationship between dental caries and IBD was further investigated. Brito et al. reported that S. mutans was detected in Crohn's disease but not in ulcerative colitis [44]. It was confirmed that Crohn's disease patients had higher decayed –missing-filled surfaces (DMFs) scores and S. mutans counts compared to the control [45]. Johannsen et al. reported that both CD and UC patients had received more dental treatment, but this was more pronounced for CD [46].

Conclusion

Oral bacteria are divided into two categories: cariogenic bacteria and periodontopathic bacteria [47]. Most of the periodontopathic bacteria are Gram-negative anaerobic and have many virulence factors associated with soft tissues and bone. It is not surprising that they affect not only the periodontal environment but also the intestine. Some of the periodontopathic bacteria, such as F. nucleatum and C. concisus , are associated with IBD and CRC. On the other hand, S. mutans is considered to be a cariogenic bacterium, and it is interesting that this bacterium also affects soft tissues of the gastric organ. The oral cavity and the intestine are not neighboring organs, but the bacteria of these organs seem to be closely associated. However, there is also the possibility that oral bacteria can only harbor bowel disease sites, and this point should be clarified. Further work by dental and medical doctors may reveal that dental and periodontal treatments decrease the incidence of IBD and CRC.

References

1. Han YW, Wang X (2013) Mobile microbiome: oral bacteria in extra-oral infections and inflammation.J Dent Res 92: 485-491.
2. Fiocchi C (1998) Inflammatory bowel disease: etiology and pathogenesis.Gastroenterology 115: 182-205.
3. Mizoguchi A (2012) Animal models of inflammatory bowel disease. In: Conn PM, editor. Animal Models of Molecular Pathology pp: 263-320.
4. Rutgeerts P, Goboes K, Peeters M, Hiele M, Penninckx F, et al. (1991) Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum.Lancet 338: 771-774.
5. Signat B, Roques C, Poulet P, Duffaut D (2011) Fusobacteriumnucleatum in periodontal health and disease.Curr Issues MolBiol 13: 25-36.
6. Feuille F, Ebersole JL, Kesavalu L, Stepfen MJ, Holt SC (1996) Mixed infection with Porphyromonasgingivalis and Fusobacteriumnucleatum in a murine lesion model: potential synergistic effects on virulence.Infect Immun 64: 2094-2100.
7. Kinder SA, Holt SC (1989) Characterization of coaggregation between Bacteroidesgingivalis T22 and Fusobacteriumnucleatum T18.Infect Immun 57: 3425-3433.
8. Kaplan CW, Lux R, Haake SK, Shi W (2009) The Fusobacteriumnucleatum outer membrane protein RadD is an arginine-inhibitableadhesin required for inter-species adherence and the structured architecture of multispecies biofilm. MolMicrobiol 71: 35-47.
9. Han YW, Ikegami A, Rajanna C, Kawsar HI, Zhou Y, et al. (2005) Identification and characterization of a novel adhesin unique to oral fusobacteria.J Bacteriol 187: 5330-5340.
10. Xu M, Yamada M, Li M, Liu H, Chen SG, et al. (2007) FadA from Fusobacteriumnucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells.J BiolChem 282: 25000-25009.
11. Verna EC, Larghi A, Faddoul SG, Stein JA, Worman HJ (2004) Portal vein thrombosis associated with Fusobacteriumnucleatum septicemia in a patient with ulcerative colitis.J ClinGastroenterol 38: 611-612.
12. Strauss J, Kaplan GG, Beck PL, Rioux K, Panaccione R, et al. (2011) Invasive potential of gut mucosa-derived Fusobacteriumnucleatum positively correlates with IBD status of the host.Inflamm Bowel Dis 17: 1971-1978.
13. Dharmani P, Strauss J, Ambrose C, Allen-Vercoe E, Chadee K (2011) Fusobacteriumnucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha.Infect Immun 79: 2597-2607.
14. Manson McGuire A, Cochrane K, Griggs AD, Haas BJ, Abeel T, et al. (2014) Evolution of invasion in a diverse set of Fusobacterium species.MBio 5: e01864.
15. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, et al. (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma.Genome Res 22: 292-298.
16. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, et al. (2012) Fusobacteriumnucleatum infection is prevalent in human colorectal carcinoma.Genome Res 22: 299-306.
17. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, et al. (2013) Fusobacteriumnucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment.Cell Host Microbe 14: 207-215.
18. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, et al. (2013) Fusobacteriumnucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadAadhesin.Cell Host Microbe 14: 195-206.
19. Warren RL, Freeman DJ, Pleasance S, Watson P, Moore RA, et al. (2013) Co-occurrence of anaerobic bacteria in colorectal carcinomas.Microbiome 1: 16.
20. Fukugaiti MH, Ignacio A, Fernandes MR, RibeiroJúnior U, Nakano V, et al. (2015) High occurrence of Fusobacteriumnucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients.Braz J Microbiol 46: 1135-1140.
21. McCoy AN, Araújo-Pérez F, Azcárate-Peril A, Yeh JJ, Sandler RS, et al. (2013) Fusobacterium is associated with colorectal adenomas.PLoS One 8: e53653.
22. Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T et al. (2014) Fusobacteriumnucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J ClinMicrobiol Infect Dis 33: 1381-1390.
23. Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, et al. (2015) Fusobacteriumnucleatum in colorectal carcinoma tissue and patient prognosis.Gut.
24. Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, et al. (2016) Association of Fusobacteriumnucleatum with immunity and molecular alterations in colorectal cancer.World J Gastroenterol 22: 557-566.
25. Holdeman LV, Cato EP, Moore WE (1984) Taxonomy of anaerobes: present state of the art. Rev Infect Dis 6: S3-10.
26. Kaakoush NO, Mitchell HM (2012) Campylobacter concisus - A new player in intestinal disease.Front Cell Infect Microbiol 2: 4.
27. Kamma JJ, Nakou M, Persson RG (2011) Association of early onset periodontitis microbiota with aspartate aminotransferase activity in gingival crevicular fluid. J ClinPeriodontol 28: 1096-1105.
28. Kalischuk LD, Buret AG (2010) A role for Campylobacter jejuni-induced enteritis in inflammatory bowel disease?Am J PhysiolGastrointest Liver Physiol 298: G1-9.
29. Zhang L, Man SM, Day AS, Leach ST, Lemberg DA, et al. (2009) Detection and isolation of Campylobacter species other than C. jejuni from children with Crohn's disease.J ClinMicrobiol 47: 453-455.
30. Zhang L, Budiman V, Day AS, Mitchell H, Lemberg DA, et al. (2010) Isolation and detection of Campylobacter concisus from saliva of healthy individuals and patients with inflammatory bowel disease.J ClinMicrobiol 48: 2965-2967.
31. Ismail Y, Mahendran V, Octavia S, Day AS, Riordan SM, et al. (2012) Investigation of the enteric pathogenic potential of oral Campylobacter concisus strains isolated from patients with inflammatory bowel disease.PLoS One 7: e38217.
32. Kovach Z, Kaakoush NO, Lamb S, Zhang L, Raftery MJ et al. (2011) Immunoreactive proteins of Campylobacter concisus, an emergent intestinal pathogen. FEMS Immunol Med Microbiol 63: 387-396.
33. Mahendran V, Tan YS, Riordan SM, Grimm MC, Day AS et al. (2013) The prevalence and polymorphisms of zonulaoccluden toxin gene in multiple Campylobacter concisus strains isolated from saliva of patients with inflammatory bowel disease and controls. PLoS One 8: e75525.
34. Zhang L, Lee H, Grimm MC, Riordan SM, Day AS, et al. (2014) Campylobacter concisus and inflammatory bowel disease.World J Gastroenterol 20: 1259-1267.
35. Burgos-Portugal JA, Mitchell HM, Castaño-Rodríguez N, Kaakoush NO (2014) The role of autophagy in the intracellular survival of Campylobacter concisus.FEBS Open Bio 4: 301-309.
36. Ma R, Sapwell N, Chung HK, Lee H, Mahendran V, et al. (2015) Investigation of the effects of pH and bile on the growth of oral Campylobacter concisus strains isolated from patients with inflammatory bowel disease and controls.J Med Microbiol 64: 438-445.
37. Mahendran V, Octavia S, Demirbas OF, Sabrina S, Ma R (2015) Delineation of genetic relatedness and population structure of oral and enteric Campylobacter concisus strains by analysis of housekeeping genes. Microbiology 161: 1600-1612.
38. Ullman RF, Miller SJ, Strampfer MJ, Cunha BA (1988) Streptococcus mutans endocarditis: report of three cases and review of the literature.Heart Lung 17: 209-212.
39. Nakano K, Hokamura K, Taniguchi N, Wada K, Kudo C, et al. (2011) The collagen-binding protein of Streptococcus mutans is involved in haemorrhagicstroke.Nat Commun 2: 485.
40. Sundh B, Emilson CG (1989) Salivary and microbial conditions and dental health in patients with Crohn's disease: a 3-year study.Oral Surg Oral Med Oral Pathol 67: 286-290.
41. Sundh B, Johansson I, Emilson CG, Nordgren S, Birkhed D (1993) Salivary antimicrobial proteins in patients with Crohn's disease.Oral Surg Oral Med Oral Pathol 76: 564-569.
42. Meurman JH, Halme L, Laine P, von Smitten K, Lindqvist C (1994) Gingival and dental status, salivary acidogenic bacteria, and yeast counts of patients with active or inactive Crohn's disease.Oral Surg Oral Med Oral Pathol 77: 465-468.
43. Kojima A, Nakano K, Wada K, Takahashi H, Katayama K, et al. (2012) Infection of specific strains of Streptococcus mutans, oral bacteria, confers a risk of ulcerative colitis.Sci Rep 2: 332.
44. Brito F, Zaltman C, Carvalho AT, Fischer RG, Persson R, et al. (2013) Subgingivalmicroflora in inflammatory bowel disease patients with untreated periodontitis.Eur J GastroenterolHepatol 25: 239-245.
45. Szymanska S, Lördal M, Rathnayake N, Gustafsson A, Johannsen A (2014) Dental caries, prevalence and risk factors in patients with Crohn's disease.PLoS One 9: e91059.
46. Johannsen A, Fored MC, Håkansson J, Ekbom A, Gustafsson A (2015) Consumption of dental treatment in patients with inflammatory bowel disease, a register study.PLoS One 10: e0134001.
47. Costalonga M, Herzberg MC (2014) The oral microbiome and the immunobiology of periodontal disease and caries.ImmunolLett 162: 22-38.