The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required.

Numerous clinical studies have concluded that BSH-active probiotic bacteria, or products containing them, are efficient in lowering total and low-density lipoprotein cholesterol. However, the mechanisms of action of BSH-active probiotic bacteria need to be further supported. There is also the need for a meta-analysis to provide better information regarding the therapeutic use of BSH-active probiotic bacteria. The future of BSH-active probiotic bacteria most likely lies as a combination therapy with already existing treatment options.

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Colorectal cancer (CRC) is the third most common form of cancer. Diverse therapies such as chemotherapy, immunotherapy and radiation have shown beneficial effects, but are limited because of their safety and toxicity. Probiotic formulations have shown great promise in CRC as preventive and early stage therapeutics. This review highlights the importance of a balanced intestinal microbiota and summarizes the recent developments in probiotics for treating CRC. Specifically, this report describes evidence of the role of probiotics in modulating the microbiota, in improving the physico-chemical conditions of the gut and in reducing oxidative stress. It also discusses the mechanisms of probiotics in inhibiting tumour progression, in producing anticancer compounds and in modulating the host immune response. Even though some of these effects were observed in several clinical trials, when probiotic formulations were used as a supplement to CRC therapies, the application of probiotics as biotherapeutics against CRC still needs further investigation. IntroductionColorectal cancer (CRC) is the third most commonly diagnosed cancer in western countries (Kumar et al., 2010). According to the Canadian Cancer Society and the National Cancer Institute, in 2012, an estimated 23 300 Canadians and 143 460 Americans were diagnosed with CRC and 9200 and 51 690, respectively, died of it. CRC develops by the accumulation of mutations, starting in stem cells at the base of the crypts (Barker et al., 2009), and usually begins as a non-cancerous polyp (Jemal et al., 2011). CRC incidence can be associated with a number of genetic factors such as germline mutations in the mismatch repair genes (Silva et al., 2009) and adenomatous polyposis coli (APC) gene (de Miranda et al., 2009). In addition to genetic predispositions, environmental factors such as lifestyle and diet play an important role in CRC risk (Steffensen et al., 1997). Researchers agree that a diet rich in red meat and processed food with a low consumption of fruits and vegetables increases CRC incidence (Ahmed, 2007; Kono, 2011). This lifestyle and diet also leads to disturbances in the intestinal environment, including the luminal content and microbiota (Zhu et al., 2011). The microbiota plays a role in generating biochemical and physiological conditions that may increase the number of colonic pre-neoplastic lesions (Rowland, 2009;Uronis et al., 2009). Interestingly, consumption of beneficial bacteria can modulate the micro-organisms of the gastrointestinal (GI) system (Prakash et al., 2011). Modulation of the unbalanced gut microbiota can provide a therapeutic and preventive effect by downgrading carcinogenic stimulating events in the colon (Rafter, 2001).Probiotics are 'live microorganisms which, when administered in an adequate amount, confer a beneficial heath effect to the host' (Ochmań ski & Barabasz, 1999;FAO/WHO, 2006). Although probiotics have been used to manage a number of GI disorders such as diarrhoea, infection and inflammation (Ehlers & Kaufmann, 2010), their role...