Probiotics and the Human Microbiome: Beyond the Gut

Probiotics
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Think you know all everything you need to understand and apply probiotics? Well, think again! We are pleased to be able to bring you a recent interview with the distinguished naturopathic physician Dr Don Brown, ND.

Naturopathic physician Dr Donald Brown is one of the leading authorities in the U.S. on evidence-based herbal medicine and the safety and efficacy of nutritional supplements and probiotics. He currently serves as the Director of Natural Product Research Consultants in Seattle, WA, sits on the Advisory Board of the American Botanical Council and was a member of the Board of Directors of the International Probiotics Association for two years.

In this interview, we will be discussing cutting edge research on the rapidly developing field of probiotics and evidence for their use in supporting the health of the gut, immune system, skin, brain, and genitourinary system.

Q. Research into the impact of probiotics on the microbiome has really exploded in the last couple of years. Why is that?

Dr. Brown: It’s ironic, talking about it as a naturopath, because we’ve always talked about the impact of the intestinal tract on health, but more recently, probiotic research has led us to realise that there are trillions of microbes in and on our body. We’re not just looking at the microbes in the gut, but the microbes in other parts of the body as well, like the skin and genitourinary tract. We have a tendency in probiotic discourse to focus on bacteria, but there are viral and fungal components of the microbiome that are natural inhabitants of the body as well. All of these microbes play an important part in our health and our wellness, and when the balance tips in the wrong direction, our health does too.

Q. So when it comes to the human microbiome, how and why do probiotic supplements work?

Dr. Brown: In thinking about the gut, I like to use the analogy of a busy parking lot. You have organisms that are health-promoting, and then you have organisms that are potential pathogens, and they’re all looking for parking spots. Bacteria have to adhere to intestinal cells to be able to either promote health or promote disease. So, one of the first things probiotic bacteria do is to compete for spots with these potential pathogens.

Then, once they set up house, the probiotic bacteria start creating a micro-environment that is inhospitable to potential pathogens by altering the pH slightly and by producing substances that are antimicrobial. They really create a situation where they say to pathogens, “Hey, this is our home, and you’re not welcome here.” They also help produce mucin and keep the tight junctions between cells in the intestinal tract healthy and intact. That’s important for intestinal barrier function, and it’s very important for preventing leaky gut.

Q. Can you give us a few examples of how probiotic bacteria support a healthy colon and our immune system?

Dr. Brown: In the colon, probiotics boost the production of short-chain fatty acids, which help with not only digestive health but the health of the body systemically. Short-chain fatty acids help to regulate inflammation in the body,[1] and butyrate, one of these acids, also has protective effects against cancer.[2] Concerning the immune system, one of the really interesting things that’s been discovered in the last ten or so years is that when these beneficial bacteria attach to the intestinal wall they communicate with certain cells in the immune system known as dendritic cells.[3] Dendritic cells are funny-looking starfish-shaped things that send feelers into the cells that line the intestinal tract. And the probiotic bacteria are actually communicating through dendritic cells to influence the production of immune mediators. Inflammatory responses are modulated through these processes as well.

Q. How broad are these effects?

“Although the microbiota can be negatively impacted by stress, it also can positively impact stress and mood, which is a whole new mechanism of action we now are beginning to understand.”

Dr. Brown: We’ve already touched on the impact on gut and immune health, And now we’re beginning to realise that the intestinal tract is communicating with the brain, through what’s called the gut-brain axis. Stress, for instance, can negatively impact the healthy bacteria in the gastrointestinal tract. The gut microbiota, in turn, modulates the stress response through the vagus nerve,[4] which goes all the way from the gut to the brain. So, although the microbiota can be negatively impacted by stress, it also can positively impact stress and mood, which is a whole new mechanism of action we now are beginning to understand. And then, there is the female genitourinary tract which also has its own population of probiotic bacteria that positively affect genitourinary tract health, possibly even helping to prevent sexually transmitted infections such as HIV.[5]

Q. What conditions have the most compelling research in terms of improved outcomes with probiotic use?

“What they’re finding is that the use of probiotics starting in pregnancy is reducing the incidence of atopic dermatitis by about 50%.”

Dr. Brown: I like to start with the things that are accepted by the medical community at large. And one of those is the fact that probiotics have a positive effect on prevention of antibiotic-associated diarrhea.[6],[7],[8] That’s a good starting point because we have really solid data that probiotics are good at preventing that.

Another area that has reached a critical mass of evidence is the prevention of atopic dermatitis [eczema] in children who are potentially at risk. The studies started in the early 2000s, looking at the mom’s risk of atopic and allergic diseases, and starting to give the mother probiotics during the second half of her last trimester.[9] Then, once the baby is born, if mom is nursing, continuing to give the probiotics to the mom until she stops. In some studies, they have provided probiotics to the at-risk infant as well.[10],[11] What they’re finding is that the use of probiotics starting in pregnancy is reducing the incidence of atopic dermatitis by about 50%. That’s amazing to me.

Q. You’ve mentioned the role of probiotics in gut health, immune health, stress responses, and the skin. What are some of the other organ systems that can be impacted by probiotics?

Dr. Brown: Another area with considerable research in the realm of probiotics is female genitourinary tract health. Conditions like bacterial vaginosis would probably be at the top of the list,[12] as well as prevention of recurrent urinary tract infections.[13] We’re finding that probiotics taken orally can populate the Vagina and produce significant effects,[14],[15] which is amazing. We used to think you’d have to administer probiotics through the Vagina, for example with a pessary, to get an effect, and that’s no longer true.

Also, studies now suggest that routine use of probiotics can reduce the incidence of upper respiratory tract infections, at least in adults.[16] There is a lot more research emerging on other conditions as well.

antibiotics image

Q. You’ve talked about antibiotics and how they disrupt the microbiome. Give us some specific examples of how probiotics may be useful with these and other medications.

“Probiotics can help break up biofilm and make standard UTI treatments perform better. And then continuing to use the probiotics, after the antibiotic course has ended, actually reduces recurrence rates of UTI.”

Dr. Brown: One of the great things about probiotics is they can be used as an adjunct to standard treatments. Take Helicobacter pylori infection, for instance. The standard triple-drug treatment for H. pylori [the bacterium associated with gastric ulcers] is very tough on people and recurrence rates are really high. As a result of the drugs, the healthy bacteria in the gastrointestinal tract are reduced by as much as 80%, but if we administer probiotics during the treatment period, it cuts the loss of “good” bacteria considerably, and if patients continue to use probiotics afterwards, they tend to bounce back more quickly.[17],[18]

Another example is urinary tract infections (UTIs). The infectious E. coli bacteria are really good at setting up what are called biofilms. It’s like they are taking a Teflon sheet and putting it over themselves. Antibiotics can reach the bacteria that are outside the protective shield, but the bacteria that are under it are not touched by antibiotics. Probiotics can help break up biofilm and make standard UTI treatments perform better.

Other examples include proton pump inhibitors, which are drugs often used for gastroesophageal reflux disease (GERD) they can have a very negative effect on the microbiome.[22] And some of the more aggressive anti-inflammatory medicines that people take may have an effect as well. We’re still in the early stages of learning which specific drugs impact the microbiome and what the effects are.


We hope that you enjoyed this really informative interview and look forward to bringing you some other expert views on different health topics very soon!


References

[1] Vinolo MA, et al. Regulation of inflammation by short chain fatty acids. Nutrients. 2011 Oct;3(10):858-76.

[2] McIntyre A, et al. Butyrate production from dietary fiber and protection against large bowel cancer in a rat model. Gut. 1993 Mar;34(3):386-91.

[3] Foligne B, et al. A key role of dendritic cells in probiotic functionality. PLoS One. 2007 Mar 21;2(3):e313.

[4] Bravo JA, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA. 2011 Sep 20;108(38):16050-5.

[5] Borgdorff H, et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J. 2014 Sep;8(9):1781-93.

[6] D’Souza AL, et al. Probiotics in prevention of antibiotic associated diarrhea: meta-analysis. BMJ. 2002 Jun 8;324(7350):1361.

[7] Sazawal S, et al. Efficacy of probiotics in prevention of acute diarrhea: a meta-analysis of masked, randomized, placebo-controlled trials. Lancet Infect Dis. 2006 Jun;6(6):374-82.

[8] McFarland LV, et al. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006 Apr;101(4):812-22.

[9] Kalliomäki M, et al. Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial. Lancet. 2001 Apr 7;357(9262):1076-9.

[10] Kalliomäki M, et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomized placebo-controlled trial. Lancet. 2003 May 31;361(9372):1869-71.

[11] Kalliomäki M, et al. Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007 Apr;119(4):1019-21.

[12] Mastromarino P, et al. Bacterial vaginosis: a review on clinical trials with probiotics. New Microbiol. 2013 Jul;36(3):229-38.

[13] Falagas, et al. Probiotics for prevention of recurrent urinary tract infections in women: a review of the evidence from microbiological and clinical studies. Drugs. 2006;66(9):1253-61.

[14] Reid G, et al. Oral probiotics can resolve urogenital infections. FEMS Immunol Med Microbiol. 2001 Feb;30(1):49-52.

[15] Petricevic L, et al. Randomized, double-blind, placebo-controlled study of oral lactobacilli to improve the vaginal flora of postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2008 Nov;141(1):54-7.

[16] Hao Q, et al. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015 Feb 3;(2):CD006895.

[17] Cremonini F, et al. Effect of different probiotic preparations on anti-Helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol. 2002 Nov;97(11):2744-9.

[18] Tong JL, et al. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther. 2007 Jan 15;25(2):155-68.

[19] McMillan A, et al. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011 Aug 1;86(1):58-64.

[20] Hanson L, et al. Probiotics for treatment and prevention of urogenital infections in women: a systematic review. J Midwifery Womens Health. 2016 May;61(3):339-55.

[21] Falagas, et al. Probiotics for prevention of recurrent urinary tract infections in women: a review of the evidence from microbiological and clinical studies. Drugs. 2006;66(9):1253-61.

[22] Imhann F, et al. The influence of proton pump inhibitors and other commonly used medication on the gut microbiota. Gut Microbes. 2017 Jul 4;8(4):351-358.

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