Key points
- The microbiota of the gut and other tissue is linked to cancer
- Evidence suggests reduced diversity of bacteria in cancer patients and distinct microbial signatures specific to the type of cancer
- Probiotics may offer some reduction in risk for certain cancers
- Probiotics reduce diarrhoea and gastrointestinal toxicity following chemotherapy and radiation treatment
The microbiota of various systems and tissue in the body is linked to the formation of cancers. For example, Helicobacter pylori and gastric cancer, and papillomavirus and cervical cancer.1 Research in children has also demonstrated that similarly to many other conditions, there is reduced diversity of bacteria in the microbiome of those with cancer and reduced levels of generally beneficial species (i.e. bifidobacteria).2 [See previous CARR articles] The interplay between the immune-inflammatory systems and the gut, and their effect on cancer control are a key target for emerging research and therapies.3
One of the largest reviews of the topic published in the Journal of Global Oncology, showed overwhelmingly (all barring one study) that there are distinct differences in the microbiota of cases and controls. The most consistent findings were for colorectal cancer and the effects of Fusobacterium species (most importantly Fusobacterium nucleatum), Porphyromonas and Peptostreptococcus which were significantly enriched in the faecal and mucosal samples of colorectal cancer patients, while 2 studies on the cervical microbiome found a decrease in abundance of the beneficial Lactobacillus crispatus in cervical cancer cases.4
There are distinct differences in the microbiota of cases and controls
Breast cancer
The microbiome of the gut is thought to play a role in the incidence of breast cancer, and research ranging from in vitro through to human suggests a role for probiotics to reduce the incidence of cancer, and tumour size and growth rates.5 Emerging research also suggests that the microbiome associated with breast tissue itself may also play a role but is poorly understood.6 The existing research has shown that breast tissue has a distinct microbiome and there is also a distinct gut bacteria of women with breast cancer.6
There is a distinct gut microbiome of women with breast cancer
Oesophageal cancer
The distribution of the gut microbiota within the gastrointestinal tract varies over time and by location in the gut. While the oesophagus had, previous to the 1990s, been thought to be mostly sterile, more recent evidence shows convincingly that there is a stable microbiome of the oesophagus and many phyla in this microbiome have been reported, including Firmicutes (e.g. Streptococcus ), Bacteroides (e.g. Prevotella ), Actinobacteria (e.g. Rothia ), Proteobacteria (e.g. Haemophilus ), Fusobacteria (e.g. Fusobacterium ), and TM7.7
One of the factors leading to oesophageal cancer is the irritation and eventual change in cell morphology of the cells of the lower oesophagus (Barret’s oesophagus). Evidence suggests that the metaplastic cells common to Barret’s oesophagus are more easily colonised by a range of bacteria, leading to greater diversity not seen in a healthy oesophagus, but including greater numbers of pathogenic bacteria.
For example, cancerous oesophageal tissue is higher in pathogenic Campylobacter and this is also associated with higher levels of pro-cancer inflammatory markers (esp. IL-6).
Cancerous oesophageal tissue if high in pathogenic Campylobacter
Porphyromonas gingivalis (implicated in periodontal disease) infects the oesophageal mucosa in squamous cell carcinoma but not tissue of healthy controls, and so, might offer promise as a biomarker for oesophageal cancers, while poor oral health is also associated with oesophageal cancer.7
Colorectal cancer
Diet is known to affect the incidence of colorectal cancers and one of the purported mechanisms for the diet-cancer interaction is by foods modifying the microbiome,8 as dysbiosis is likely to increase the risk of cancer.1 In particular, fibres and resistant starch, and nutrient-dense foods (especially dense in bioflavonoids), modify the microbiota and are linked to reduced rates of colorectal cancers in observational studies.8 There are differences in the microbiota of people with colorectal cancer compared to controls, and in particular, species like Clostridium septicum, Enterococcus faecalis, Streptococcus bovis, Bacteroides fragilis, Helicobacter pylori, Escherichia coli and Fusobacterium spp. are purported to play a role in colorectal pathogenesis and bacteria from genera Fusobacterium, Porphyromonas, Bacteroidetes and Prevotella are increased in faecal and biopsy analysis of colorectal cancer patients.1
There are differences in the microbiota of people with colorectal cancer compared to controls
In addition, there is a 60% increase in mortality post-surgery associated with high levels of Fusobacterium nucleatum (and also possible hazard associated with the bacteria Bacteroides fragilis).9
Prebiotics and colorectal cancer
Both animal research and observational studies of humans suggest a link between prebiotic fibres and starches and reduced rates of colorectal cancer. A 2012 review of trials on the effects of prebiotics on markers of colorectal cancer, found that lactulose might reduce adenoma recurrence. Resistant starch had no effect on adenoma or cancer development but crypt mitotic location, gene expression, and DNA methylation were somewhat improved after resistant starch consumption.10
Research suggests a link between prebiotic fibres and starches and reduced rates of colorectal cancer
Genitourinary cancers
The evidence tends towards suggesting a role for the microbiota in increasing risk for genitourinary cancers.11 The microbiome is thought to help reduce the incidence and effect of pro-cancer pathogens (such as Schistosoma haematobium bladder infections and nitrosamine-producing bacteria).
Fusobacterium, Sphingobacterium, and Enterococcus bacteria may be more prevalent in the urinary microbiome of people suffering pathologies that are linked to the development of cancer and Fusobacterium, Actinobaculum, Facklamia, and Campylobacter are found in greater abundance in those with genitourinary cancers compared to higher levels of Veillonella, Streptococcus, and Corynebacterium in healthy controls.11
Fusobacterium, Actinobaculum, Facklamia, and Campylobacter are found in greater abundance in those with genitourinary cancers
In bladder cancer, Thermoactinomycetaceae was increased in cancer patients, and Sphingobacteriaceae increased in controls. 11
Kidney cancer
Urinary tract infections are thought to increase the risk of developing kidney cancer. There are likely to be links between infection, the microbiota of the genitourinary tract, and cancer, and the microbiome offers possibilities for treatment both for testing and intervention (with, for example, probiotics or microbial transplants) but at this time, there is little evidence for the efficacy of either in genitourinary tract cancers.
Prostate cancer
Higher levels of Bacteroides were found in the faecal and urinary microbiomes of people with prostate cancer.12
Probiotics and cancer treatment
Several investigations have demonstrated mechanisms by which probiotic treatment can reduce the incidence and severity of cancer, including perhaps most importantly, immune, and inflammatory modulation, reduced DNA damage, and the inhibition of pathogenic and carcinogenic microflora in the gut. There is also a range of other mechanisms by which probiotics might aid cancer treatment, including reducing pro-carcinogen enzyme activity, binding of carcinogens and mutagens (for metabolism and excretion), and increased short-chain fatty acid production. Most extensively studied and efficacious are likely to be lactobacilli and bifidobacteria, but there is no clear consensus on types and strains that should be used and dosages, along with effects in immunocompromised individuals and different forms of cancer.13, 14
Most extensively studied and efficacious are likely to be lactobacilli and bifidobacteria
In research on breast cancer in vitro models, probiotic intervention induces cell-death of cancer cells and inhibits their proliferation, while in animals, probiotics inhibit tumour growth and reduce tumour size.5 In humans, probiotic treatment, and higher intakes of fermented dairy products (esp. Lactobacillus casei Shirota) reduced breast cancer incidence.5
Relatively strong evidence demonstrates that probiotic treatment can reduce diarrhoea, gastrointestinal toxicity, and fever in cancer treatment,15-17 and research on women with gynaecological cancers, chemo- and radiotherapy reduce bacterial diversity and modify the microbiome to one consistent with toxicity and gastrointestinal distress.18 While most studies show relative safety, case reports are highlighting the potential for increased bacterial and fungal loads in the blood of those taking probiotics.16
Higher intakes of fermented dairy products (esp. Lactobacillus casei Shirota) reduced breast cancer incidence
A recent (2019) meta-analysis has looked into the available data on the effects of probiotics on diarrhoea in people receiving radiation therapy. In 8 trials (1116 total participants), probiotics were associated with a significant reduction in diarrhoea[i] and anti-diarrhoeal medication[ii] without significant differences in watery stool, or those receiving both chemotherapy and radiation therapy.19 However, another analysis of the effect of probiotic therapy on chemotherapy-induced diarrhoea suggested a greater than 50% reduction[iii] in the incidence of diarrhoea with probiotic treatment vs placebo.20 There is a trend towards reduced gastrointestinal toxicity (mucositis, enteritis) that accompanies chemotherapy and radiation treatment from probiotic supplementation, especially with Lactobacillus species (rhamnosus, acidophilus) and bifidobacteria at dosages of least 1 billion CFU per day.15
Probiotics reduce the incidence and severity of diarrhoea accompanying cancer treatment
Probiotics also show promise for reducing rates of infection[iv] after surgery for colorectal cancer,21 and significantly decrease inflammatory factors, chemotherapy side effects, severe diarrhoea, postoperative infectious complications, duration of antibiotic therapy, and shift the faecal microbiota in favour of beneficial Actinobacteria.22
Also, the oral probiotic Lactobacillus salivarius is likely to offer protective benefits against oral cancers,23, 24 and probiotics are also likely to reduce rates of infection post-treatment.24
It should, however, be remembered that different cancer types and cells both intra- and interindividual can vary considerably and the effects of any nutritional intervention can vary depending on the type of cancer and the individual, and temporally, and additional investigation is necessary to further elucidate this.25
Traditional and herbal medicines, the gut, and cancer
A range of prebiotic fibre-containing foods like yams, along with various phytochemicals from common and medicinal herbs (i.e. sage and mint, Boswellia serrata, liquorice, St John’s wort), fruits (hesperidin from citrus) and sulforaphane and sulforaphene from cruciferous vegetables (esp. broccoli sprouts), curcuminoids from turmeric, and mushrooms like Reishi (Ganoderma sp.) and Lion’s Mane (Hericium sp.) have shown promise for modulating the microbiota and improving outcomes in animal models of cancer and colitis.26
Mushrooms like Reishi and Lion’s Mane have shown promise for modulating the microbiota and improving outcomes in animal models of cancer and colitis
References
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[i] Risk ratio (RR) = 0.62 (95% CI: 0.46-0.83)
[ii] RR = 0.54 (95% CI: 0.35-0.84)
[iii] Odds ratio (OR) = 0.47 (95% CI: 0.28-0.76; p = 0.002)
[iv] OR = 0.51 (95% CI: 0.38–0.68, p < 0.01)
