Integrative medicine: the evolving story of the human microbiome

February 2015
BY Victor S. Sierpina, MD, ABFM, ABIHM, Director, Medical Student Education Program, WD and Laura Nell Nicholson Family Professor of Integrative Medicine, Professor, Family Medicine University of Texas Distinguished Teaching Professor

A few weeks ago, I served as a panelist and speaker on a pre-conference workshop on Probiotics at the annual Scripps Natural Supplements Conference in San Diego. This is the premier conference held each January that covers emerging clinical, research, and regulatory issues related to herbs and natural supplements. Put it on your CME calendar for next year.

During our panel presentations, a number of themes and issues emerged which I will touch on briefly. Some key items were: the effect of diet on our microbiome: how alterations in gut bacteria can produce endotoxemia, inflammation, and glucose intolerance; alterations in gut bacteria contribute to obesity; fecal transplants are good for resistant Clostridium dificile and even ulcerative colitis; antibiotics significantly deplete the microbiome species variation and this dysbiosis can have long- term health consequences well beyond simple antibiotic-induced diarrhea; no- calorie soft drinks alter gut biota which might account for why weight loss is not robust and diabetes risk are not lowered by these beverages.

Much research on the microbiome is emerging and like studies into the human genome, is revealing not only what we have newly discovered, but also the large gaps in what we don’t know in this area.

First, we all are colonized with gut bacteria at birth. It turns out that Cesarean born infants do not get the same kind of inoculum of bacteria as those birthed vaginally. Some suggestions from the pediatric literature are that the long-term consequences of this may be related to atopic diseases, asthma, and inflammatory conditions, in general, perhaps even obesity and childhood diabetes. Bottle fed as compared to breast fed babies likewise develop a different microbiome because of essential prebiotics in mother’s milk that are not duplicated in formula. Again, this is another reason to encourage breastfeeding.

Our microbiome extends from our oral cavity to lower intestine with increasing colony counts of bacteria the further we go down the gastrointestinal tract. The sheer numbers of bacterial species and their volume are astonishing. Microbiome species number over a thousand, 80% of which cannot be cultured. The weight of these is 3-6 pounds, making the microbiome on of the bodies largest “organs. And here is a real surprise: the amount of bacterial DNA in our body exceeds human DNA by 150 times. You might even say they are the organism, and we are just the medium!

Without these commensal bacteria, we could not digest many foods, especially the cellulose and other components of plants that are essential to our health. Bacterial fermentation breaks these down into usable short chain fatty acids and sugar molecules that can be absorbed and utilized.

It turns out that through human history, we have ingested lots of bacteria both from the soil and due to fermentation of foods. Prior to refrigeration, the only practical way to preserve many foods included fermentation. As a result we have wine and beer, cheeses, yogurt, kefir, sauerkraut, olives, pickles, honey, kim chee, poi, miso, tempeh, and other kinds of culturally derived preserved foods. All of these are sources of probiotics and the fermentation aids in their digestibility.

Now, we also have available probiotics in encapsulated forms. These can be helpful in conditions such as antibiotic associated diarrhea, irritable bowel disease, ulcerative colitis, viral and traveler’s diarrhea, and many inflammatory conditions that have developed due to breakdown of the tight junction barriers in the gut from disruption of normal commensal biofilms. These breakdowns occur from many drugs such as NSAID’s, steroids, proton pump inhibitors, chemotherapeutic agents, and radiation therapy as well as antibiotics.

Feeding our gut bacteria lots of plant materials is a way to reduce inflammation, as well as reducing glucose intolerance. Studies have even shown a relation between gut bacteria and several neuropsychological conditions, the so-called gut-brain connection.

At this point, we have a long way to go to understand fully and utilize probiotics therapeutically. What species, what doses, what brands to use, how long to treat and so on are to a large extent unknowns. With improved RNA and DNA testing, we can now fingerprint the array of gut bacteria in our microbiome, and this may allow for better specificity in terms of treatments in the future.

For example, we know that Saccharomyces boulardi, a yeast, is helpful in treating antibiotics resistant Clostridium dificile and that Lactobacillus reuteri is efficacious in treatment-resistant bacterial vaginosis. High dose VSL#3 containing around 500 billion colony forming units of probiotics has been demonstrated as effective in patients with ulcerative colitis and pouchitis.

The usual dose of probiotics in yogurt by comparison is around 1 billion CFU’s or less. The tendency of clinicians who use probiotics is increasing doses, e.g. 30-100 billion CFU’s for IBS. I commonly give 10- 20 BU to patients treated with antibiotics to prevent dysbiosis, starting during the antibiotic treatment, spacing dosing at least two hours from the antibiotic and continuing for 3-4 weeks afterward. This is more of an art than a science at this stage.

However, it is an evolving science. From studies on fecal transplants, dietary influences on gut bacteria and inflammation, and the enormous trove of bacterial DNA in our microbiome, keep tuned to what is turning out to be an enormously important field in health and healing. I predict human clinical studies of the microbiome well beyond many recent revealing rodent experiments will provide us a health related yield comparable to what we are learning in genomics.