Colorectal cancer (CRC) refers to tumours that start in the colon and spreads all the way to the rectum. Different types of colorectal polyps exist, but CRC usually develops from adenomas. CRC is one of the very common causes of mortality among patients with cancer worldwide including developed and undeveloped countries but mostly in first world countries. It is predicted that by 2035, over 25 million incidences of CRC will be discovered on a yearly basis.1 It is also estimated that over 376 000 new cases of CRC diagnosis as well as approximately 200 000 deaths take place yearly in China.2
CRC proves to be a silent killer ailment that may not be noticed in time until the cancer has progressed significantly. Symptoms of CRC resemble symptoms of several ailments and is easily misdiagnosed unless a colonoscopy is done. The symptoms of CRC include unexplained anaemia, unexplained weight loss, bloating, changes in the bowel movement habits, bloody stool, vomiting and pelvic pain. It has been proven that the initiating events of CRC include TP53 mutation in CRC associated with colitis as well as mutation in sporadic CRC.3 Different causes of CRC have been examined over the years from data collected in cohort-based studies and these findings resemble studies carried out in animal models, The common conclusion is that age, lifestyle choices such as smoking and excessive alcohol intake which can lead to obesity or diabetes, as well as genetic risk factors, contribute to the development of CRC.4 5
CRC can also be inherited through the genes by inheriting mutated genes that trigger tumour growth, but this only accounts for about 5% of CRC cases.6 In addition, different researchers in their studies have agreed that an increased number of opportunistic bacteria which quickly turn pathogenic, such as Helicobacter pylori, Bacteroides fragilis, Helicobacter hepaticus, enterotoxigenic Escherichia coli, Fusobacterium nucleatum and Streptococcus bovis, can lead to the initiation of adenomas formation that lead to CRC.7
Patients with CRC usually undergo surgery to remove cancerous polyps or to remove some part of their colon which have been affected (colon resection). Others undergo chemotherapy or radiotherapy to treat CRC. These treatment options are sometimes unsuccessful or lead to a myriad of severe side effects which increase hospital stay time and sometimes morbidity.8
Probiotics is redefined by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as ‘live microorganisms which when administered in adequate amounts, confer a health benefit on the host’.9 Probiotic microorganisms are special because they are capable of surviving in the human gastrointestinal tract before they get to the colon, where the majority of their metabolic activity is carried out. They include lactic acid producing bacteria of the genera Lactobacillus and Bifidobacterium as well as Propionibacterium, Saccharomyces and are the major ingredients in yoghurts and other functional foods such as unfermented milks, cheese, kefir and fermented milk.10
On the other hand, prebiotics are usually termed as non-digestible carbohydrates such as inulin and oligosaccharides, soy and resistant starch. Prebiotics is defined by ISAPP as ‘a substrate that is selectively used by host microorganisms to confer health benefit to the host’.9 Prebiotics stimulate an increased growth of probiotics by providing a more favourable environment for their growth.11 Leading to a gut environment that promotes the competitive dismissal of opportunistic and potentially pathogenic bacteria which could initiate the beginning of CRC.11 Several studies have shown that the administration of both probiotics and prebiotics as a combination can aid increasingly in improving the conditions of patients with CRC especially after colorectal surgery has been performed.12 13
Probiotics have been used by the traditional healers for the prevention and treatment of different types of illneses from the simple stomach ache to intestinal neoplasia. In addition various experimental studies have shown that continious ingestion of probiotic bacteria can enhance the qualitative as well as quantitative components of the gut microbiota.14 In one instance, the ingestion of Lactobacillus acidophilus LA-11, L. plantarum CGMCC 1258 and Bifidobacterium longum BL-88 (2.6×10 14 (CFU)/day) for 16 days, resulted in an increase in the diversification of gut microflora and microbial richness in patients suffering from CRC who have been scheduled for colorectomy. Eventually, the microbial flora makeup of these individuals improved to resemble that of individuals without CRC.15 Probiotic bacteria when consumed in adequate quantittes are able to diminish the total quantity of non beneficial disease causing bacteria found in the colon by numerous mechanisms, particulary as regards; rivalry for nutrients, growth factors, and adhesion of the probiotics onto the intestinal cells of the host.16 Ingestion of probiotic also inhibits the activity of pathobionts such as Clostridium perfringens and Klebsiella pneumonia which are potential pathogenic microorganisms and could also be symbiotic microorganisms under certain gut environment conditions.17 Some probiotic bacteria can produce antibacterial substances such as bacteriocins, hydrogen peroxide, lactic acid and reuterin, which decrease the growth or totally eradicate pathogenic bacteria from the colon. The very popular advantages of the consumption and use of probiotics in the management and treatment of diarrhoea associated to anti-cancer chemotherapy revolves around the restoration to normal of the intestinal microbiota.18 The favourable altreation by probiotic bacteria in the makeup of the gut microbiome is closely associated with the reduced risk of suffering from CRC in the future.19 Production of short chain fatty acids by probiotics which leads to cell apoptosis is one of the aways through which probiotics reduce the proliferation of colorectal carcinaoma.20 Scientific eveidence by various in-vitro and in-vivo studies have concluded that various strains of probiotics possess anti-carcinogenic properties via different mechanisms.21 22
Based on our search on systematic reviews related to our topic, we found out that most of the systematic reviews which have been done were not entirely specific to CRC,12 and those that are specific to probiotics and patients with CRC focus on one outcome either on postoperative complications,23 surgical site infection,24 diarrhoea from chemotherapy.25 We see this as a limitation of these studies, hence we intend to study more than one outcome in order to get a holisitc idea of how probiotics administration affect patients with CRC who are receiving different types of treatment on different levels. As we will asses several outcomes, these outcomes will be categorised and discussed based on if they are primary or secondary outcomes. Previously published reviews related to probiotics mostly investigated its effect on CRC and the mechanisms through which probiotics ameliorate CRC using diverse models including pre-clinical studies, and in-vitro studies.26 27 Some reviews also focused more on the use of specific probiotic as anticancer adjuvant.28 Our systematic review is unique and different from other reviews in which we intend to include only randomised clinical trial studies (RCT) and asses the effects of the adminstration of various types of probiotics on patients with CRC.
To systematically review, assess and summarise and interpret clinical trials studies on how the use of probiotics compared with placebo in patients with CRC in helps in the treatment, and management of CRC. In addition, this study will critically summarise how probiotics administration in patients with CRC affect the diversity of gut microbiome and patient quality of life.
This systematic review protocol goes in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines.29
The inclusion criteria include studies on patients with CRC who are were treated with chemotherapy, radiotherapy or surgery. The included studies must be carried out as randomised controlled trials with either a comparator group, control group or placebo group. Details of the inclusion and exclusion criteria that will be used in the systematic review is in table 1.