Probing the mysteries of probiotics

In the human body, microbes outnumber human cells 10 to 1.

That sounds icky, but the news isn’t all bad: Bacteria can help us and may have even more potential than we currently know.

Sarkis Mazmanian, a biologist at the California Institute of Technology,received a MacArthur Foundation “genius grant” to study good vs. bad bacteria in the gut. He and colleagues have postulated that this bacteria can train the immune system to distinguish between “foreign” microbes and the ones that originate in the body.

Our symbiotic relationship with bacteria may help prevent and treat autoimmune diseases such as multiple sclerosis and Alzheimer’s, they say. By studying this microbiome of gut bacteria, Mazmanian is laying a knowledge foundation for potential new therapies to treat many human diseases.

CNN spoke with Mazmanian about his research and why he thinks bacteria could one day be prescribed as a medical treatment. The following is an edited portion of that interview.

CNN: First of all, what are good bacteria, or probiotics?

Sarkis Mazmanian: The definition of probiotic bacteria is that they’re live bacteria that confer some sort of health benefit, but that doesn’t imply their source. And I think this is a relevant issue because most of the probiotics that are found in either health food stores or in yogurts in supermarkets are organisms that were isolated many decades ago and were cultured for very arbitrary reasons. They weren’t tested for their health benefits; they were isolated because they were very stable organisms. In other words, companies could grow them and then put them on the shelf and ship them around.

Over the decades, people cultured them to put them in pills. It’s a several-billion-dollar industry now. But the issue here is that none of those organisms were ever tested in animals and certainly not in clinical trials while they were being developed.

CNN: Does this include Lactobacillus acidophilus that a lot of people use as dietary supplements?

Mazmanian: Yeah, all the Lactobacilli and bifidobacteria species. And also Saccharomyces yeast, so it’s not just bacteria; there are yeast that are considered probiotics.

It’s only been the last 10 years that there’s been a growing appreciation, which has really skyrocketed the last five years, for the fact that these organisms may actually confer health benefits, and so the entities who have commercialized probiotics are now going back and testing whether or not there are benefits to those commercially available probiotics.

These are ongoing studies, and you have to modify studies and find the right conditions and indications, but the jury is still out on those organisms. … As we sit here today, there’s really no strong evidence that those organisms do confer any health benefits. There’s no evidence that they’re bad for you, so I think that should be very clear. People (are) taking probiotics – I do take probiotics myself – just sort of on the hope that there might be some health benefits, but there is certainly no evidence that there are any negative health ramifications of probiotics.

But now, there’s such a growing interest in the microbiome and gut bacteria, people are now isolating organisms. And we’ve done this, and this is why I got that award (the MacArthur Foundation “genius grant”) was that we were the first group to identify an organism that comes from humans – not dairy products – that has demonstrable health benefits in both mice and in human cells, and we hope to someday give this to humans clinically to treat various indications.

And those may be organisms that I think, through evolution, have found a way to interact with their hosts and might ultimately be beneficial, either as nutraceuticals in health food stores, but they would not be Lactobacillus; they would be other organisms.

Someday, you might go to the doctor, and the doctor may prescribe a pill, and in that pill may be a microbe or a collection of microbes that have met FDA standards upon which you can make health claims based on that treatment.

CNN: How do probiotic bacteria get into the gut in the first place? Is it true that our guts are basically sterile before we’re born, and just as soon as we come into the world, we’re colonized?

Mazmanian: Correct. Our initial exposure to microbes comes from the birth canal. So we are sterile in utero. And as we’re born, we’re exposed to microbes from our mothers initially. Over the first year or two of life, we assemble the rest of the organisms.

There are ongoing studies that are not definitive, but what we tend to believe is that there are many organisms that come from our mothers and others that we obtain from the environment, meaning another human or mammal. And that’s an important distinction because the microbes that live in our gut are not the same organisms that live in soil or on your coffee table.

The organisms that live in our gut are finely adapted and finely tuned to only live in that environment. So there’s no consensus on where they come from, because it’s probably going to be different for different people. We’re acquiring and losing microbes in a chaotic stage in the first two years of life, and by 2 years, it reaches a stability that’s reminiscent of the adult microbiome.

CNN: What is the new organism you’re working with called?

Mazmanian: The organism is called Bacteroides fragillis. As I mentioned, it’s a human organism, and it’s found in other organisms as well, but it’s found in a subset of humans, not all. We are all different in our microbial species, and Bacteroides fragillis is found in 15% to 20% of the population.

But that being said, it doesn’t mean that those who don’t have the organism are not protected or do not have health benefits. There’s a tremendous amount of redundancy in our microbiome – our gut bacteria – so those who don’t have B. fragillis will have another organism that would be beneficial to them.

CNN: Some people have claimed probiotics can even help people with neurological diseases, like multiple sclerosis and autism, even down to skin conditions like eczema. What exactly does your gut bacteria have to do with your nervous system?

Mazmanian: People are beginning to make links between gut bacteria and the nervous system, and this is an area we’re very interested in, but I would caution (against making) any conclusions yet.

It’s very early in the field and the research to think that an organism is going to correct something like autism or Alzheimer’s or schizophrenia or some of the other things being talked about. It’s not a critique on the investigators, but this is how research works, is that you have to build a foundation upon which you grow the knowledge.

Secondly, all the experiments have been done in mice, and mice are not humans, but they are a very good surrogate for humans. So we really need to take the results with a grain of salt.

CNN: In Western society and in many other parts of the world, we want everything to be sterile, and we think of ourselves as separate from nature. Sitting all day indoors at desks typing on computers, we forget our true connection to nature and how we can’t function without these other, more primordial creatures.

Mazmanian: You just described my life, sitting in front of the computer all day. If you just think about our lifestyles, just take the last couple of hundred years, relative to even just a couple of thousand years of how much time we spend indoors, of how much processed foods we eat, of how much we’ve changed our sanitation.

Think about how we go to the bathroom and our interaction with fecal matter. When we lived in forests and caves, we were possibly being re-exposed to our own gut microbes. I think that is how humans evolved. And there was a lot of cross-fertilization between people, and groups would cross-colonize each other.

In a very short period of time, not only do we not spend enough time outdoors and get exposed to sunlight and vitamin D, but we’ve broken that cycle of being exposed to our own microbes and other people’s microbes.

There’s a price to pay for that. There’s a price to pay for affluence, and that is presumably we’re losing these health benefits, which results in a default of increased diseases.

CNN: So what can we do in our “office culture” to help our immune systems and populate our guts?

Mazmanian: Well, this is what we’re trying to do. No one’s going to go back to the previous way of life, and no one would advocate for that.

If we’re smart enough to understand what those microbes are doing, and if we are not narcissists in thinking that we don’t need those microbes, then what we can hopefully achieve is a better understanding of what those microbes are doing and which ones are doing what, in order to supplement our diets, or finding other ways to associate ourselves with those microbes that have health benefits.