Streptococcus gallolyticus bacteraemia and colorectal neoplasia: an old association with a new name

Clinical record

A 63‐year‐old man presented with headache, fever and decreased conscious state. He was initially treated for bacterial meningitis with intravenous antibiotics. His cerebrospinal fluid culture was negative. However, his blood culture isolated Streptococcus gallolyticus (previously: Streptococcus bovis) identified by mass spectrometry. The patient was referred for a colonoscopy, which showed a 3 cm pedunculated polyp in the sigmoid colon (Box 1, A). This advanced polyp was snared (Box 1, B) and, on histology, revealed a tubulovillous adenoma with high grade dysplasia but clear margins. The patient was subsequently booked for a repeat colonoscopy in 3 years as per the recommendations of Cancer Council Australia.1

Discussion

Colorectal cancer development is influenced by both genetic and environmental factors. Among environmental risk factors, there is increasing recognition on the role of intestinal microbiota in colorectal cancer. One microorganism associated with colonic neoplasia is S. bovis, a group D streptococcus that is found throughout the gastrointestinal tract, particularly the colon, in 2.5–15% of asymptomatic individuals.2 It is associated with other gastrointestinal malignancies, including the oral cavity, duodenum, gallbladder and pancreas.2 It is an opportunistic pathogen that can cause bacteraemia and infective endocarditis in adults.2 Since the first description of the association between S. bovis and colorectal neoplasia in 1951, multiple studies have been published supporting this relationship.3,4,5 There are varying reports on the frequency of colorectal tumours, ranging from 25–80% in patients with S. bovis bacteraemia to 18–62% of patients with S. bovis endocarditis.3 With the introduction of taxonomic changes in 2003 to the S. bovis group (Box 2),6 it was found that not all subspecies of S. bovis have a strong association with colonic neoplasia.3 A meta‐analysis reported that patients with S. bovis biotype I (S. gallolyticus subsp gallolyticus [SGG]) bacteraemia and infective endocarditis have a statistically significant increase in the risk of colorectal cancer compared with patients with S. bovis biotype II.3 In contrast, the incidence of colorectal cancer among patients with S. bovis biotype II does not appear higher than the general population.3 Interestingly, patients with SGG bacteraemia have a stronger association with villous or tubulovillous adenomas than carcinomas.3,4 The lesion appears to be mostly located in the distal colon.2

Whether this association represents cause or effect is uncertain. The “driver–passenger” theory2 was proposed to explain the role of microbiota in colorectal carcinogenesis. This model describes the “driver” bacteria causing mutations by inducing DNA damage with genotoxins, while the “passenger” bacteria have mechanisms providing them growth advantage in tumour environments. SGG possesses collagen‐binding proteins and pili that preferentially adhere to colorectal mucosa and endocardium.2,4 Studies show SGG selectively colonises tissue in colorectal cancer, and the organism has been identified inside tumours rather than on mucosal surfaces.2 Animal models have shown that SGG may play a role in the adenoma–carcinoma sequence by acting as a driver of early paraneoplastic lesions.2,4 SGG secretes a specific bacteriocin that enhances colonisation by killing other commensals.2 Moreover, new lesions develop in the colon within 2–4 years after SGG infection. These findings suggest that SGG has a driver and passenger role in colorectal cancer carcinogenesis.2 This mechanism has also been shown in bacterial species such as Fusobacterium nucleatum, Enterococcus faecalis and colibactin‐producing Escherichia coli, which are also implicated in colorectal cancer.2 Surface proteins by F. nucleatum allows adherence and invasion to cells, whereas colorectal cancer‐causing E. coli produces colibactin causing epithelial damage.2

It is important to note that the lack of uniform nomenclature and genotyping of SGG limits its characterisation and role in the development of colorectal cancer. More detailed analysis in clarifying subtypes of SGG is required to further understand their malignant potential. There needs to be greater awareness from clinicians and researchers about these taxonomic changes and use this nomenclature consistently in clinical practice and research publications.

Clinicians need to appreciate the strong association of SGG infection and colorectal cancer. The finding of this organism in blood cultures should prompt a colonoscopy for early diagnosis of colorectal cancer. However, if tumours are not found in the first instance, patients should be scheduled for endoscopic surveillance, as colonic tumours may develop several years later. Presently, there are no current guidelines on the follow‐up interval, but patients should be treated as high risk cases (eg, colonoscopy within 3 years).

Box 1 – Colonoscopic image of the sigmoid colon demonstrating the 3 cm pedunculated polyp (A) and the sigmoid polyp snared at the base (B)

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