Many different biomarkers indicative of different mechanisms of activity have been used in probiotic studies relating to cancer.
The research for L. casei Shirota ranges from genotoxicity tests to retrospective epidemiological studies, as well as human intervention studies, showing:
• Reduction of human papillomavirus infection rate (Verhoeven et al. 2012)
• Positive clinical outcomes predominantly in colorectal cancer (Ishikawa et al. 2005) and bladder cancer (Aso et al. 1992, Aso et al. 1995), but there are also positive outcomes relating to cervical cancer (Verhoeven et al. 2012), breast cancer (Toi et al. 2013), biliary and liver cancer (reduction of post-operative infections) (Eguchi et al. 2010, Kanazawa et al. 2005, Sugawara et al. 2006), lung (Masuno et al. 1991), and uterine cancer (Okawa et al. 1989, Okawa et al. 1993).
The effect of a synbiotic, containing L. casei Shirota alongside a prebiotic, has also been investigated in oesophageal patients receiving chemotherapy (Mootori et al. 2017).
Worldwide colorectal cancer (CRC) is the third most common cancer in men and the second in women (Ferlay et al. 2015). Whilst several aspects of lifestyle play a role in this cancer’s aetiology, it is now widely believed that components of the intestinal microbiota may be involved in CRC carcinogenesis. The following long-term clinical trial is a highlight of the broad range of cancer studies with L. casei Shirota.
Study: Colorectal Cancer
Effect on CRC tumours (four-year trial) - Ishikawa et al. (2005) Int J Cancer 116:762-767.
Method: In this randomised trial, 398 subjects who had previously had at least two colorectal tumours removed, were assigned for four years to one of the following dietary interventions: (i) dietary advice with consumption of wheat bran (7.5 g three times a day); (ii) L. casei Shirota (1010 viable cells/g three times a day as powder); (iii) both; or (iv) neither. Consultations occurred every three months. The primary endpoint was presence or absence of new tumours after two and four years’ intervention, detected by colonoscopy.
Results: After two years, multivariate adjusted OR (95% CI) for tumour occurrence was 0.76 (0.50-1.15) for the L. casei Shirota group but 1.31 (0.87-1.98) in the wheat bran group. After four years, in the L. casei Shirota group a significant decrease was observed for occurrence of colorectal tumours with moderate to severe atypia (OR 0.65, 95% CI 0.43-0.98). Wheat bran consumption resulted in a significantly higher incidence of tumours > 3mm. Groups consuming wheat bran plus L. casei Shirota had lower tumour occurrence compared to those without any intervention, but higher compared to those on single dietary intervention.
Conclusions: The authors concluded that intake of L. casei Shirota appeared to suppress development of colorectal tumours. There was a statistically significant association between probiotic consumption and reduced risk of development of tumours with moderate to severe atypia.
L. casei Shirota research relating to bladder cancer includes epidemiological and human intervention studies. For example a retrospective case-control study by Ohashi et al. (2002) compared 180 bladder cancer cases with 445 population matched controls in relation to ingestion of milk fermented with L. casei Shirota over the past 10-15 years. A negative correlation was found, indicating habitual intake of the lactic acid bacteria was associated with lower risk of bladder cancer.
Study: Bladder Cancer
Effect on recurrence of superficial bladder cancer - Aso Y et al. (1995) Eur Urol 27:104-109.
Method: This randomised, double-blind, placebo-controlled trial involved 138 patients who had undergone previous transurethral resection of bladder cancer. Prior to randomisation, they were stratified according to those with primary multiple tumours, those with recurrent single tumour, and those with recurrent multiple tumours. For one year or until tumour recurrence, subjects consumed either (i) 1 g of powder containing 1 x 1010 CFU of L. casei Shirota three times daily or (ii) a placebo.
During the study period, no other anti-cancer therapy was given. Tumour recurrence was monitored by quarterly cytological analysis of urine and endoscopic analysis. Routine haematology, biochemistry and urine tests were conducted before surgery at enrolment, at one and three months after enrolment, and thereafter every three months.
Results: Compared to placebo, L. casei Shirota was more effective in reducing risk of tumour development in patients with primary multiple tumours and those with recurrent single tumours but not in patients with recurrent multiple tumours.
When data from patients with primary multiple tumours and with recurrent single tumours were combined for analysis, this showed that the 50% recurrence-free period was longer in the probiotic group (688 days) compared to the control (543 days), which was equivalent to a 1.3-fold increase in time (P = 0.08). Multivariate life-table analysis of this combined group also showed a significantly better outcome for those on probiotic (P = 0.01) as well as a trend for slowing the rate of tumour.
Conclusions: The authors concluded that the L. casei Shirota preparation was safe and might help reduce the risk of recurrence of superficial bladder cancer.
HPV & cerival cancer risk
Globally, cervical cancer is the fourth most common cancer in women (Ferlay et al. 2015). Cervical cancer is associated with infection by a member of the family of human papillomaviruses (HPV): HPV-DNA can be found in 99.7% of all cervical cancers. Low-grade squamous intraepithelial lesions are closely associated with infection with certain high-risk HPV; the clearance of both shows a close temporal relationship (Syrjänen 2007).
Study: HPV & Cervical Cancer
Effect on HPV-associated pre-cancerous abnormalities (adults) - Verhoeven V et al. (2012) Eur J Cancer Prev 22(1):46-51.
Method: This open-label, controlled study in Belgium investigated whether L. casei Shirota could influence clearance of HPV infection and associated pre-cancerous abnormalities (low-grade squamous intraepithelial lesions; LSIL). For six months, the researchers followed 54 women diagnosed with HPV+ LSIL in their PAP smear, who had been allocated to take either a daily fermented milk drink with L. casei Shirota or no intervention. Efficacy was assessed by comparing PAP smear and HPV status, at baseline and after six months.
Results: The women in the L. casei Shirota group had twice as high a chance of cytological abnormalities becoming cleared (P=0.05) compared to the control group. HPV was cleared in 29% of the L. casei Shirota group compared to 19% in the control group (P=0.41).
Conclusions: The authors concluded that this indicated that L. casei Shirota promotes clearance of HPV-related cytological abnormalities, a potentially new way of managing cervical cancer precursors.
Study: Breast Cancer
Breast cancer incidence: effects of soy isoflavone and L. casei Shirota - Toi M et al. (2013) Curr Nutr Food Sci 9(4):194-200.
Method: Aiming to evaluate how consumption of beverages containing L. casei Shirota and/or soy isoflavone since adolescence affected the risk of later developing breast cancer, this population-based case-controlled study matched 306 women with breast cancer and 662 controls aged 40-55 years. Diet, lifestyle and other breast cancer risk factors were analysed by means of self-administered questionnaire and interview.
Results: The odds ratio of regular L. casei Shirota consumption (more than 4 times per week) for breast cancer was 0.65 (P=0.048). Furthermore, the greater the consumption of soy, the lower the odds ratio of breast cancer became.
Conclusions: The authors concluded that regular consumption of L. casei Shirota and soy isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women.