Probiotics: Manipulating Your Internal Ecosystem

The human body is an ecosystem harboring numerous different species living in delicate balance, well-adapted to each other and to their physical environment. The creatures that thrive on our skin and in our noses, mouths, urogenital tracts and guts are microscopic organisms – mainly bacteria, fungi and bacteriophages (viruses carried by bacteria).  These organisms comprise the human “microbiome” and perform valuable services for us, breaking down food, making vitamins and other chemical compounds that we absorb, teaching our immune systems how to recognize invaders, and maintaining bowel health.  Their genes interact with our genes, up-regulating and down-regulating them as we change our diets.

Research relating the the invisible world of the microbiome to physical states of health and illness is still in its infancy, but has produced interesting data and useful observations about attempts to restore microbiome composition after disruption by illness and antibiotics. Outside this world of esoteric research, entrepreneurs have leapt ahead of the facts, supplying millions of people who wish to better their health with supplements called probiotics, pills containing “living microorganisms, which when administered in adequate amounts, confer health benefits on the host.

Not a new idea

The idea of manipulating the body’s microorganisms to improve health is not new. In 1908, Nobel prize winner Elie Metchnikoff, the “Father of Immunology,” theorized that the large intestine was a cesspool where putrefaction by bacteria produced autotoxins that aged the body. While some believers advocated removing the colon or administering repeated enemas to cleanse it, Metchnikoff thought that Lactobacilli, bacteria found in the yogurt consumed by long-lived Bulgarians, could  battle the putrefactive bacteria, and that consumption of the yogurt, along with other ascetic practices like avoidance of alcohol and intoxicants, would prevent dementia, illness and premature death. Like yogurt, other fermented, bacteria-laden foodstuffs such as kefir and sauerkraut have long been advocated for general good health.

Experimental evidence?

There is tantalizing experimental evidence that the interior microbial world has previously unsuspected ties to overall health. For instance, in germ-free mice, introduction of specific bacteria into the gut will alter energy usage because the bacteria digest incoming food.  The mice get fatter on the same amount of food they were fed in the germ-free state because they absorb more of it. Bacteria also produce substances which act like neurotransmitters and communicate with the brain via the gut’s neural network. And they modify the action of their genes to match the types of food we eat, which in turn modifies food absorption and immune system function.

Genetic tools speed modern microbiome research

High speed DNA analysis is the modern tool which drives microbiome research. No longer do scientists struggle with culturing and identifying the multitude of bacterial types that reside in the human body. Based on microbial DNA sequencing of samples from human bodies, we know that we carry over 3.3 million bacterial genes, vastly more than our own 22,000 genes). There is far more diversity between humans in terms of the genetics of the organisms they carry than there is in their genetic profiles – and enough stability in each person’s microbiome to create unique microbial DNA profiles, which can be identified like fingerprints on surfaces people touch. There are even identifiable differences between the fingerprint profiles from an individual’s right and left hands.

Fecal transplants: the ultimate probiotics

The best scientific information about manipulation of the microbiome in the quest for better health comes from the ultimate type of probiotic – the so-called fecal transplant. Transfer of fecal material from one person’s gut to another’s was first tried in the 1950s. In this experiment, a patient suffering severe colitis was spared surgical removal of the colon when restoration of a normal mix of bacteria, as well as everything else in contained in the stool sample used for the transplant, quelled the toxic bacteria eating away his colonic lining.  Since that time, fecal transplantation has been 90% successful in treating the severe and often recurrent colitis and diarrhea produced by the bacterium clostridium difficile.

The complex nature of fecal material

Fecal material contains bacteria, viruses, bacteriophages – the viruses that bacteria can transfer among themselves and to the host, other types of microorganisms, and all the chemical products of the metabolic processes of all these living creatures. Each stool donor has a unique microbial profile, as does each fecal transplant recipient. Donor stool is screened for drug resistant and abnormal bacteria, prepared as a slurry and introduced into the colon via colonoscope, or into the stomach or small intestine via a tube. Capsules that resist the acid and enzymatic environment of the upper GI tract also show some promise.

Probiotics: less complex mixtures of living organisms than fecal transplants

Like fecal transplants, probiotics aim to create a healthier balance of bacteria in the gut, but they are capsules containing a few types of freeze-dried bacteria harvested from cultures in labs. When swallowed and exposed to the warmth and moisture of the body’s interior they spring to life. Sold as supplements, probiotics are not subject to FDA quality control.

Probiotics have been studied as treatments for antibiotic-induced diarrhea, allergies, autism, metabolic syndrome, autoimmune ulcerative colitis, Crohn’s, disease, infectious colitis, constipation, traveler’s diarrhea, periodontal disease, and more. The studies are fraught with problems that make most of them inconclusive at best. But as preventives for antibiotic0induced diarrhea and clostridium difficile diarrhea, probiotics may be helpful and are generally not harmful for otherwise healthy people.  Theoretically, people with depressed immune systems could contract an infection from one of the organisms included in the product. There has been at least one neonatal death attributed to a contaminated probiotic.

Do the introduced bacteria survive?

A recent, carefully designed study from Israel assessed whether or not probiotic bacteria took up residence in the colon after ingestion. In some people, called persisters, the probiotic bacteria can be found in the recipient, but in others, called resisters, none of the probiotic bacteria survive. The type of bacterial populations already living in the gut make the difference. In addition, another good study demonstrated that probiotic use actually delayed the return of normal bacteria to the colon after a course of antibiotics.

Much work remains in the investigation of  the human microbiome and in attempts to improve health by manipulating it. What is clear so far is that each person’s microbiome is unique and that success in understanding and manipulating it will require individualized evaluation. Most probiotic use at this time is a one-size-fits-all approach, done for non-specific reasons. Similar to Metchnikoff’s Bulgarian yogurt.*

*modern science shows that the lactobacillus in the yogurt does not survive the trip through the gut to the colon.

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