Health benefits of probiotic bacteria
Although the full health benefits of probiotics have not been completely determined the results of published studies are increasingly compelling. The benefits of a healthy flora of bacteria (microbiome) relate to the gut itself but also to improve general well-being and reduce the progression an incidence of degenerative and inflammatory disease outside the gut. Although, again more research is needed, ingestion of healthy probiotic bacteria along with fibre and polyphenol rich foods are major contributors to a healthy micro biome:
Potential benefits for the gut and digestion.
Travellers diarrhoea. Certain strains of probiotics have demonstrated positive results in treating diarrhoea and gastroenteritis commonly caught whilst travelling, usually from drinking water. In particular, a study published in the Journal of Pediatrics, concluded that Lactobacillus species are a safe and effective form of treatment for children with infectious diarrhoea. Other studies, have shown that prophylactic use of Lactobacillus containing probiotics significantly reduced the risk of nosocomial diarrhoea in infants, especially nosocomial rotavirus gastroenteritis.
Antibiotic induced diarrhoea. Antibiotics are obviously vital to kill unhealthy bacterial infection but, as a side effect, they also reduce the healthy bacteria in our gut altering natural balance of the microflora which can lead to bloating and diarrhoea. A report published in the Journal of Pediatric Gastroenterology and Nutrition showed that probiotics were helpful in the prevention or treatment of, antibiotic induced diarrhoea especially in children.
Bacterial food poisoning. Most acute diarrhea episodes are caused by viruses but some, especially those caught by ingesting infected food, can be bacterial. A study published in the prestigious scientific journal Proceedings of the National Academy of Sciences, found that probiotic bacteria can help protect against bacterial infection including Listeria and the super bug Clostridium difficile infection. Some Hospitals are giving people probiotics before going into hospital to reduce their risks of infection.
Chemotherapy induced diarrhoea. Some chemotherapy agents commonly cause diarrhoea due to damage to the cells lining the gut. If severe, as well as being very distressing and uncomfortable for the patient, this can lead to dehydration, concentration of the chemotherapy in the blood stream and eventually renal damage. A placebo controlled randomised trial from Helsinki involving 5FU chemotherapy for bowel cancer showed a highly significant reduction in the risk of diarrhoea. Other trials have reported benefits for analogues of 5FU such as capecitabine. Several ongoing trials are underway across the world including a large and significant one from Washington University School of Medicine.
After chemotherapy: Even without diarrhoea a course of intense chemotherapy can cause significant damage to the gut microbiome leading to multiple problems including malabsorption, fatigue and inflammation. Many oncologists and nutritionist are feel that restoring the gut flora with a good quality probiotic is a good is a good idea and some research even suggest autofaecal transplant! (see paper)
Radiotherapy bowel problems: Several well conducted trials have demonstrated that probiotics could help prevent radiation bowel damage and certainly help recovery after radiotherapy – click here for an example of a published trial
Irritable bowel syndrome (IBS) is a condition associated with abdominal bloating and flatulence. A 2010 Cochrane review summarised the evidence from clinical studies which showed that probiotics can help in some people. The National Institute for Health and Care Excellence (NICE) recommends taking them for at least four weeks, at a dose recommended by the manufacturer and if they work – continually.
Wheat and Lactose intolerance. As you get older it is common to develop an intolerance of gluten found in wheat and other grains. This causes IBS like symptoms with bloating and colicky pains. In the first instance it is advisable to reduce the intake of bread, pasta and cereals but a number of studies have demonstrated a helpful effect for probiotic intake. Intolerance to milk also is becoming more common, usually the result of a lactase deficiency. Lactase is an enzyme normally produced in your small intestine. It is needed to break down lactose and to enable you to digest milk. The probiotic Lactobacillus acidophilus helps with the digestion and absorption of lactose by producing lactase.
Potential benefits outside the gut.
Upper respiratory tract infections (colds). A study from Australia gave healthy athletes either probiotics or placebo. After one year the probiotic group had less colds and as a consequence had less disruption to their training. Athletes in Australia and across the world now take probiotics regularly. Several studies have shown that regular intake of live lactobacilli and bifidobacteria, shortened the duration and severity of upper respiratory tract infections. In 2011 a summary of all international studies was published in the prestigious Cochrane Database of Systematic Reviews, and concluded that probiotics also reduced the incidence of upper respiratory tract infections. The economic implications of these findings are enormous as the impact of colds is estimated to cost the United States $40 billion each year!
Bone health. Probiotics bacteria have been shown to reduce gut inflammatory markers and there is a known link between chronic gut inflammation and bone health. In A number of laboratory studies, just 4-6 weeks of probiotics significant increase in bone density in animals with establish osteoporosis or prevented its development [Chiang, Yacon, Ohlsson]. There have been some trials in adolescence looking at pro and prebiotics calcium uptake which suggest increases in bone density [Abrams] and many authors are suggesting benefits for different age groups, which may well be the case although it would be advantageous to confirm this with randomised trials [Reid].
Chronic inflammation. A chronic over active immunity leads to excess inflammatory cytokines which can cause numerous chronic diseases including arthritis, dementia, cancer and heart disease. Although the Mediterranean diet is good the best anti-inflammatory diet is know has the macrobiotic diet which has lots of fermented foods such as miso soup, kefir and kimchi. UK diets are traditional low in these bacteria rich foods.
Brain function. A study involving mice conducted by the Alimentary Pharmabiotic Centre in University of Cork showed that mice fed with Lactobacillus had significantly fewer stress, anxiety and depression-related behaviours than those fed with just broth. Moreover, bacteria fed mice had lower levels of the stress-induced hormone, corticosterone and had altered expression of receptors for the neurotransmitter GABA in the brain. In humans, a study from The University of California, showed that healthy women consuming probiotic-containing yogurt were reported to have improved brain function and less environmentally induced markers of stress.
Blood Pressure. There is emerging evidence that probiotics may have a role in cardiovascular health. A meta-analysis of nine studies, published in the journal Hypertension, tracked over 543 adults with both normal and high blood pressure and found that taking probiotics lowered systolic blood pressure by 3.56 mmHg and diastolic blood pressure by 2.38 mmHg, on average. The greatest effects were seen in subjects with BP above 130/85. And those who took probiotics with multiple strains were more successful at lowering BP than single-strain sources.
Fatty liver and metabolic syndrome. Too much fat accumulating in the liver affects its function, eventually leading to damage. Several factors can cause a fatty liver, defined as fat stores >10% of its volume, including obesity, diabetes, alcohol abuse, poor diet and genetic susceptibility. Although there are no significant studies in humans, researchers recently discovered that Lactobacillus and Bifidobacterium probiotic strains prevented the accumulation of fat in the liver of obese rats. Markers of inflammation (tumor necrosis factor and interleukin 6) and triglyceride counts also improved. In another animal study, mice were fed a high fat diet for eight weeks and given probiotics or placebo. Mice who received the bacteria ate significantly less than the control mice, had lower insulin levels and body fat, and reduced their fatty liver deposits. Trials in humans are planned.
Obesity Obese patients usually have a poor microflora which promotes inflammation and storage of fats leading to further weight gain.A number of studies have demonstrated that some probiotics taken before a meal reduce overall calorie intake and reduce longer term body mass index [Hume]
Cholesterol levels. Research presented at the American Heart Association’s Scientific Sessions in 2012 reported that a formulation of Lactobacillus may be able to reduce blood levels of LDL (bad cholesterol).
Chronic Fatigue Syndrome. Scientists at University of Cork reported in the journal Gut Microbes that Bifidobacterium may have benefits for patients with chronic fatigue syndrome.
Probiotics gut health and cancer
While it is clear than more research is needed, evidence so far strongly suggests that a diverse bacterial microbiome can protect us from cancer by:
- Outcompeting (displacing) cancer-causing pathogens
- Reducing inflammation
- Priming immune responses
There is growing evidence that the immune responses to gut bacteria seem to help stimulate immune responses against cancer. In addition, through molecular cues, such as cytokine IL-10, beneficial gut bacteria can dampen down inflammation and strengthen anticancer T-cell responses not only in the gut but throughout the body.
Preliminary experiments in animals found that a stimulated growth of bifidobacteria in the colon lead to the inhibition of colon carcinogenesis. It was suggested that this was attributed to the pH-lowering effect of bifidobacteria in the colon, which subsequently inhibited the growth of E. coli and clostridia. A decrease in growth of such pathogenic microorganisms also produce the modulation of bacterial enzymes that convert pro-carcinogens to carcinogens. In humans taking regular probiotics been linked to a lower rate of new polyp formation and bowel cancer relapse.
Healthy gut bacteria also produce butyrate that stimulates immune attach against cancer via T cells and helper T cells. Butyrate also exerts a direct effect on cancer cells, by turning off genes involved in cell growth and turning on genes that trigger cell suicide (apoptosis). Early research showed that butyrate can block the growth of colon cancer cells in vitro, and experiments in mice suggest that dietary intake of probiotics and/or prebiotics with soluble fiber may increase butyrate production and slow tumor development. Besides fibre, gut bacteria can use other dietary sources, particularly polyphenols, to produce a range of cancer-preventive chemicals:
- anti-inflammatory urolithins are produced from ellagic acid found in pomegranates.
- antioxidant equol is produced from daizdein found in soy-based foods.
- anti-inflammatory and cancer-blocking isothiocyanites are produced from glucosinolates found in broccoli.
- anti-inflammatory conjugated linoleic acid is produced from linoleum acid, a component of vegetable oils.
A fibre and polyphenol rich diet can increasing the abundance of cancer-preventive, butyrate-producing bacteria in the gut. High-protein, low-carbohydrate diets on the other hand may change fermentation in the intestine, leading to increased levels of harmful nitrosamines, and decreased levels of protective molecules like butyrate and phenols. Other research suggests that a high-fat diet can change the microbiome in a way that increases bacterial production of the bile acid DCA, which promotes colon and oesophageal cancers.
The microbiome and response to cancer treatments:
Laboratory and clinical studies are revealing a fascinating role for gut bacteria. The gut microbiome helps enhance the efficacy of immunotherapy. Scientists have recently discovered that particular species of gut bacteria increase the therapeutic benefit from CTLA-4 blockade (Bacteroides) in melanoma, while others enhance the effect PD-1 blockade (Clostridiales) and PD-L1 blockade (Bifidobacterium).8,9-11 These insights suggest that individual differences in microbiome composition may be one of the reasons these immunotherapies work better in some people than others.11,12
Scientists have a theory to explain the beneficial effects of gut bacteria during cancer treatment. Chemotherapy (cyclophosphamide and platinum salts) and immunotherapy can damage the intestinal lining, allowing certain types of gut bacteria and bacterial byproducts to leak into the blood circulation. Once they reach lymph nodes and lymphoid organs, these bacteria prime Th1 and Th17 T cells, which help recruit other immune cells to the tumor.
Microbiome Remodeling – A Possible New Strategy Against Cancer
Microbiome research is a young, but fast-growing field. It is clear from animal and early clinical studies that the effect of the microbiome on cancer should not be discounted. While there are still many open questions, in the not so distant future, cancer care will likely include an analysis of the patient’s microbiome at diagnosis to inform personalized treatment planning. It may also be possible to manipulate the microbiome to optimize treatment outcomes.
- Bultman SJ: The microbiome and its potential as a cancer preventive intervention. Semin Oncol 43:97-106, 2016Schwabe RF: The microbiome and cancer. Nat Rev Cancer 13:800-12, 2013
- Viaud S. Gut microbiome and anticancer immune response: really hot Sh*t! Cell Death Differ 22:199-214, 2015
- Shahanavaj K: Cancer and the microbiome: potential applications as new tumor biomarker. Expert Rev Anticancer Ther 15:317-30, 2015.
- Russo E: The interplay between the microbiome and immune response in cancer development. Therap Adv Gastroenterol 9:594-605, 2016.
- Pevsner-Fischer M: Role of the microbiome in non-gastrointestinal cancers. World J Clin Oncol 7:200-13, 2016
- Poutahidis T: Gut microbiota and the paradox of cancer immunotherapy. Front Immunol 5:157, 2014
- Zitvogel L et al: Microbiome and Anticancer Immunosurveillance. Cell 165:276-87, 2016
- Gopalakrishnan V: Association of diversity and composition of the gut microbiome with differential responses to PD-1 based therapy in patients with metastatic melanoma. J Clin Oncol 35, 2017
- Vetizou M : Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350:1079-84, 2015
- Sivan A: Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1. Science 350:1084-9, 2015
- Pitt JM: Fine-Tuning Cancer Immunotherapy: Optimizing the Gut Microbiome. Cancer Res 76:4602-7, 2016
- Prevention of irinotecan-induced diarrhea by probiotics: Randomized double-blind, placebo-controlled phase III study. J Clin Oncology. Mego M et al 32:5s, 2014 (s 9611).
- Hume M et al Prebiotic supplementation improves appetite control in children with overweight and obesity: a randomized controlled trial. Am J Clin Nutrition 2017. 22, 2017, doi: 10.3945/ajcn.116.140947
- Abrams SA et al Effect of prebiotic supplementation and calcium intake on body mass index. J Pediatr. 2007;151(3):293-8.
- Health claims substantiation for probiotic and prebiotic products. Sanders M et al. 2011, Gut Microbes, 2 (3), 127-133.
- Safety assessment of probiotics for human use. Sanders M, Akkermans L et al 2010 Gut Microbes, 1 (3) pp 164-185.
- Probiotics: From Bench to Market. Annals of the New York Academy of Sciences (2010) Klein M, Sanders M, Duong T DOI: 10.1111/j.1749-6632.2010.05839.x
- Guide to designing, conducting, publishing and communicating results of clinical studies involving probiotic applications in human participants. (2010) Gut Microbes Shane A, Michael D. Cabana M et al, Vol 1 (4) pp 243-253.
- Food Formats for Effective Delivery of Probiotics. Annual Review of Food Science and Technology. 2009 Saunders M and Marco M. Vol. 1: 65-85.
- How Do We Know When Something Called “Probiotic” Is Really a Probiotic? A Guideline for Consumers and Health Care Professionals (2009).
- Saunders M: Probiotics: Their potential benefit to human health. J of the council for ag science and tech 2011 Oct 2011.
- Probiotics in the management of chemo induced diarrhoea. JPEN J Parenter Enteral Nutr 2009. 33 (5) 569-70.
- Chiang S et al. Antiosteoporotic effects of Lactobacillus -fermented soy skim milk on bone mineral density and the microstructure of femoral bone in ovariectomized mice. J Agric Food Chem. 2011, 27; 59(14):7734-42
- Yacon F et al Bifidobacterium longum modulate bone health in rats. J Med Food. 2012; 15(7):664-70.
- Ohlsson C et al Probiotics protect mice from ovariectomy-induced cortical bone loss. PLoS One. 2014; 17; 9(3):e92368.
- Reid G et al. New scientific paradigms for probiotics and prebiotics. J Clin Gastroenterol. 2003; 37(2):105-18.
- Delia et al Probiotics and radiotherapy bowel damage. World Journal of Gatroenterology. 2007; 13(6), 912