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BMJ Case Rep. 2010; 2010: bcr06.2009.2019.
Published online Jan 13, 2010. doi:  10.1136/bcr.06.2009.2019
PMCID: PMC3028456
Novel treatment (new drug/intervention; established drug/procedure in new situation)
Effect of Lactobacillus casei on Streptococcus bovis in faecal flora
Atsuko Kawano,1 Hideki Ishikawa,2 Ikuko Akedo,3 Tomiyo Nakamura,4 Kazumasa Matsumoto,5 Hiroo Takayama,5 Akemi Imaoka,5 Yoshinori Umesaki,5 Ryuichiro Tanaka,5 Toru Otani,6 and Toshiyuki Sakai2
1Osaka Medical College, Division of Preventive and Social Medicine, Department of Hygiene and Public Health, 2-7 Daigakutyo Takatsuki City Osaka, Takatsuki, 569-8686, Japan
2Kyoto Prefectural University of Medicine, Department of Molecular-Targeting Cancer Prevention, 2-17 Imahashi, 3-chome Tyuo-ku, Osaka City, Osaka, 541-0042, Japan
3Osaka Medical Center for Cancer and Cardiovascular Diseases, Gastroenterology, 1-3-3 Nakamichi Higashinari-ku, Osaka, 537-8511, Japan
4Osaka University, Pathology, School of Allied Health Science, Faculty of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan
5Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi, 186-0011, Japan
6Otani clinic, 1-4-2-205 Nakamichi Higashinari-ku, Osaka, 537-0025, Japan
Hideki Ishikawa, cancer/at/gol.com
Abstract
Bacteraemia caused by Streptococcus bovis is often associated with colorectal tumours. Also, experimental studies have been proposed that S bovis acts as a promoter of tumours. We report the case of a man with colon adenoma who had a high proportion of S bovis in his faecal flora. He was treated with a Lactobacillus casei preparation (BLP) and the effect on the faecal flora was examined. L casei reduced the proportion of S bovis (from 43% down to 9%), and the effect continued after the administration of BLP was stopped. Our data indicate that BLP can repress the excessive colonisation of S bovis.
Background
Endocarditis and bacteraemia caused by Streptococcus bovis infection are associated with colorectal neoplasms.1,2 We report the case of a patient with colon adenomas who had a high proportion of S bovis in his faecal flora. Since it has been proposed that Lactobacillus casei can modify intestinal bacterial flora by raising Bifidobacterium and reducing Enterobacteriaceae,3 the patient was treated with an Lactobacillus casei preparation (BLP), containing 1×1010/g of live L casei Shirota, in an attempt to improve his faecal flora.
A 53-year-old man, who had been cured of colon carcinoma following a colonoscopic procedure in 1990, visited the Department of Gastroenterology, Osaka Medical Center for Cancer and Cardiovascular Diseases, in 1993 to remove a recurrent polyp. He had a pedunculated polyp in his ascending colon which was resected by endoscopic mucosal resection technique. The size of the head of the polyp was 14×8×7 mm. Histologically, it was a tubular adenomatous polyp with moderate atypia. After informed consent was obtained, the patient was enrolled into the Interventional Trial for Colorectal Cancer Prevention in Osaka.4 One of the baseline tests of the trial was an examination for faecal flora 1 month after resection of colorectal polyps. The patient collected his faeces using an airtight plastic bag with free-oxygen absorbing agent and brought it to our hospital, while it was kept cool with ice. After measuring the pH immediately by using a pH meter (Horiba pH meter F-8), the faeces was sent to Yakult Central Institute for Microbiological Research for culture within 36 h after collection. The flora analysis was done by the anaerobic roll tube method or aerobic agar plate method. In our case, the proportion of the number of the genus Streptococcus against whole faecal flora was so high that we identified this bacterium as S bovis using the API Strep identification system (API System SA, France). For reference, the composition and percentage (average and standard deviation) of faecal flora of 125 patients with two or more colorectal neoplasms 1 month after endoscopic resection is shown in table 1. The proportion of the genus Streptococcus in whole faecal flora was around 43% in this case, while the total percentage of other genera (excluding Bifidobacterium and Enterobacteriaceae) was <1%.
Table 1
Table 1
Change in the amount of bacteria in the faecal flora during administration of Lactobacillus casei preparation (BLP)
After obtaining the patient’s informed consent, administration of BLP (three times a day after each meal) was started with the aim of improving of his intestinal flora. Six months after administration of BLP, the percentage of Streptococcus was reduced from 43% to 9%; moreover, the lowered percentage of Streptococcus compared with baseline was maintained for 2 years after the administration of BLP was stopped (table 1, fig 1). Other genera, except Enterobacteriaceae and Bifidobacterium, did not show any specific changes (table 1). The proportion of Enterobacteriaceae was reduced by the administration; however, these bacteria rebounded up again after BLP was stopped. On the other hand, Bifidobacterium increased during the administration period, but dropped sharply after the treatment was stopped. Faecal pH was unrelated to the change in the faecal flora. Any side effects by BLP or any change of bowel movements were not recognised. Follow-up colonoscopy after 4 years revealed a pedunculated polyp in the transverse colon, 7 mm in diameter, which was shown to be a tubular adenoma with moderate atypia upon histological examination.
Figure 1
Figure 1
Change in the proportion of Streptococcus bovis, Bifidobacterium and Enterobacteriaceae in the faecal flora following the administration of Lactobacillus casei preparation (BLP). The proportion of S bovis following BLP treatment was relatively low compared (more ...)
Outcome and follow-up
The patient has undergone follow-up colonoscopy every 2 years. There has been no recurrence of the colorectal tumour so far. Also, he has not contracted endocarditis, bacteraemia, or sepsis.
The first description of colorectal cancer occurring in association with S bovis bacteraemia was attributed to Mccoy and Mason in 1951. S bovis is known to be a causal bacterium of endocarditis and accounts for approximately 15% of bacterial endocarditis.1 Many reports regarding an association between endocarditis or bacteraemia due to S bovis and colorectal cancer have been published.1,2 The patients with endocarditis caused by S bovis more frequently suffered from colorectal cancer than those patients infected with other causal bacteria.1 Burns et al5 reported that patients with colorectal cancer have S bovis in their faeces more frequently than healthy people. Klein et al2 reported that the faecal carrier rate of S bovis was significantly higher in patients with colorectal cancer or inflammatory bowel disease than in controls, while an association between S bovis and the colorectal cancer could not be recognised by Dubrow et al.6
It has been proposed that S bovis could readily survive in the intestines of patients with colorectal neoplasms and that S bovis itself might produce carcinogens.2 Kampe et al7 considered that colorectal neoplasms have the portal site for the entry of S bovis. More recently, it was reported that S bovis and antigens extracted from the bacterial cell wall acted as a promoter of early pre-neoplastic lesions in the colon of rats.8 Moreover, the antigens extracted from S bovis have been shown to induce interleukin 8 (IL-8), prostaglandin E2 (PG-E2), and cyclo-oxygenase 2 (COX-2) production by using human colorectal cancer cells (Caco-2 cells) and mucosal tissue of rats.9
BLP is a preparation of live L casei Shirota (freeze dried bacterium), containing 1×1010 bacteria/g, which are resistant to acid, digestive juice and bile acid. L casei reaches the colon alive, and improves gastrointestinal flora by raising Bifidobacterium and reducing Enterobacteriaceae.3 Our case appears to confirm the effect of BLP on Bifidobacterium and Enterobacteriaceae. BLP also suppresses harmful bacteria such as S bovis. The mechanism of this effect is suspected to depend on the antibacterial activity of lactic acid and the promotion of an immune reaction induced by BLP, such as the activation of macrophages and the production of interferon.10
In conclusion, we were able to reduce the proportion of S bovis in the patient’s faecal flora by treating him with BLP for 6 years, and this effect continued for at least 2 years after BLP administration was stopped. This is the first report of successful manipulation of S bovis in the faecal flora. However, further studies will be necessary to determine whether any benefit is derived from the reduction of S bovis in the flora.
Learning points
  • The case is presented of a patient with colon adenoma, who had a high proportion of Streptococcus bovis in his faecal flora.
  • Endocarditis and bacteraemia due to S bovis infection are associated with colorectal neoplasms.
  • The patient was treated with Lactobacillus casei Shirota strain (L casei) which resulted in a reduction in the proportion of S bovis (from 43% down to 9%), and this effect was continued after the treatment was stopped.
  • This is the first report of successful manipulation of S bovis in the faecal flora.
Footnotes
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.
1. Gupta A, Madani R, Mukhtar H. Streptococcus bovis endocarditis; a silent sign for colonic tumour. Colorectal Dis 2009 Feb 17. [Epub ahead of print] [PubMed]
2. Klein RS, Recco RA, Catalaano MT. Association of Streptococcus bovis with carcinoma of the colon. N Engl J Med 1977; 297: 800–2. [PubMed]
3. Tanaka R, Owaki M. A controlled study of the effect of the ingestion of Lactobacillus casei fermented milk on the intestinal microflora, its microbial metabolism and the immune system of the healthy humans. The 12th symposium of intestinal flora, presented by Riken Gakkai-Shuppan Center, Tokyo. 1994: 85–104.
4. Ishikawa H, Akedo I, Suzuki T, et al. Interventional trial for colorectal cancer prevention in Osaka: an introduction to the protocol. Jpn J Cancer Res 1995; 86: 707–10. [PubMed]
5. Burns CA, McCaughey R, Lanter CB. The association of Streptococcus bovis fecal carriage and colon neoplasia; a possible relationship with polyps and their premalignant potential. Am J Gastroenterol 1985; 80: 42–4. [PubMed]
6. Dubrow R, Edberg S, Wikfors E, et al. Fecal carriage of Streptococcus bovis and colorectal adenomas. Gastroenterology 1991; 101: 721–5. [PubMed]
7. Kampe CE, Vovan T, Alim A, et al. Streptococcus sanguuis bacteremia and colorectal cancer: A case report. Med Pediat Oncol 1995; 24: 67-8. [PubMed]
8. Ellmerich S, Schöller M, Duranton B, et al. Promotion of intestinal carcinogenesis by Streptococcus bovis. Carcinogenesis 2000; 2: 753–6. [PubMed]
9. Biarc J, Nguyen IS, Pini A, et al. Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S. bovis). Carcinogenesis 2004; 25: 1477–84. [PubMed]
10. Asahara T, Takahashi M, Nomoto K, et al. Assessment of safety of lactobacillus strains based on resistance to host innate defense mechanisms. Clin Diagn Lab Immunol 2003; 10: 169–73. [PMC free article] [PubMed]
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