09/01/2012 01:25 am ET Updated Oct 31, 2012

Our Place in Nature, and Vice Versa

We have long known that bacteria living on and in our bodies outnumber our cells -- which themselves sum up to a number that exceeds any hope of real understanding -- by 20 to one. We are a rounding error in our own skin.

And we have increasing evidence of the profound influence of these intimate neighbors on far more than just digestion. They are increasingly implicated in collaboration with us in almost every aspect of our physiology, exerting particularly noteworthy effects on immune system function and hormonal balance. There is increasing evidence that they may have something to do with the prevalence of obesity, or at least those cases of it associated with particular resistance to weight loss.

We have also long known that the particular cells of the immune system responsible for inflammation in allergy and asthma, called eosinophils, are the cells on which the body calls to fight parasites. Other cells preferentially get the call for dealing with viruses (lymphocytes), or pathogenic bacteria (neutrophils).

And we have long seen a pattern in global epidemiology that hints at something profound about our place in nature, and nature's place in us. By and large, societies that still have parasites to contend with don't have allergies or asthma. Societies, such as ours, burdened by allergy and asthma, have mostly banished our parasites -- such as the various worms that would otherwise take up residence in our gastrointestinal tracts.

All of this is time-honored knowledge. But it is inviting the evolution of new thinking. Maybe parasites aren't all bad.

It may be that the inverse association between parasites and asthma isn't true, true, and unrelated, but actually about cause-and-effect. In the simplest of potential explanations, it may be that when eosinophils are busy doing the job for which they were intended, they don't have the opportunity to loiter in the lungs and cause trouble. It may be that when an immune system has real work to do, it doesn't get all worked up over pollen. Humans cannot be pollinated; pollen is not a genuine threat.

The plot quickly thickens thereafter. If immune system idleness leads to pollen-related mischief, it may underlie far more serious pathologies as well.

Autoimmune diseases are diverse and widespread, and in the aggregate account for a huge portion of the disease burden in modern societies, an enormous toll of misery, astronomical costs, and highly prevalent disability. The category includes conditions ranging from multiple sclerosis, to rheumatoid arthritis, to inflammatory bowel diseases.

What we know of autoimmune diseases, and it's not nearly enough, attributes them to a case of mistaken identity. The fundamental job of the immune system is to defend "us" from "them," "them" being all foreign material in the universe that could attempt to invade our personal space, and would represent a threat were it to do so.

You can well imagine there is no reasonable means to inventory all "foreign material in the universe." So the body has applied the far more manageable approach of simply inventorying itself.

All of our cells bear proteins on their surface, called histocompatibility antigens. That's a long word, but there's an easy way to think of them: initials in your underwear at sleep-away camp. If you go to sleep-away camp (or boarding school, or college), and you wind up in a communal laundry situation, you certainly don't want to memorize what everyone else's underwear looks like. Just mark your own -- and know that everything else is foreign. That's how the immune system works.

But unfortunately, those proteins on our own cells and the proteins on some foreign invaders can look an awful lot alike -- just as someone else can have the same initials as you. When the immune system is provoked to respond to the one, it may mistakenly go after the other. And so it may be that an invader of some kind that really isn't very dangerous comes, and goes -- and leaves the immune system bogged down in a case of mistaken identity, chronically attacking some part of our own body it now misreads as foreign.

While I am not an immunologist, I do deal with autoimmune conditions in my patients enough to have devoted considerable thought to the vexing problem they pose. My musings on the topic have run to "recognition enhancement vaccines," essentially a form of immunization we could use to help the immune system distinguish more faithfully between native and foreign.

Such an approach is used in computer systems to identify fingerprints, for instance. If two prints that look alike are not reliably differentiated by the software, a higher-powered image of an area of noteworthy distinction is fed into the computer -- which then reliably tells the two apart. Such an approach does not yet exist for autoimmunity in us, but I believe it could.

But much creative thinking is now devoted to another approach altogether: getting down and dirty with nature.

There is very little inflammatory bowel disease in parts of the world where bowels accommodate helminths. Or in plain English: worms.

There are now some studies indicating a potential therapeutic benefit of introducing such parasites as a treatment for inflammatory bowel disease. Other studies suggest comparable benefit for diverse autoimmune diseases, such as MS, having nothing obviously to do with the bowel. And since inflammation underlies the most prevalent chronic diseases of all -- heart disease, cancer, and diabetes -- a potential link there, too, is well within the bounds of current thinking.

The mechanisms of such benefit remain a topic of conjecture. Parasites influence the regulation and responses of the immune system, may alter the integrity of the gut lining, and may simply occupy immune cells otherwise at liberty to cause trouble. It's all a work in progress, as are the relevant therapeutic options.

For now, the use of probiotic bacteria in capsule form as a therapeutic modality for such conditions as irritable bowel syndrome is increasingly routine. We make extensive use of probiotics and related products in my clinic.

The use of therapeutic parasites is not yet routine, or even routinely accessible -- but movement in that direction no longer looks implausible. We have much yet to learn about the optimal balance between distancing ourselves from the dangers of predation by such means as antibiotics and hygiene, and accommodating the ecological equilibrium of which we are an indelible part, and to which we are adapted.

On the topic of antibiotics and indelible linkages, there is a fascinating addendum to this column courtesy of Italian sausage. A recent study indicates that antibiotics used routinely in livestock leave residues in the meats from which sausages are made, that in turn kill bacteria used intentionally in the making of sausage, and responsible for a fermentation process that in turn kills other bacteria, such as E. coli and salmonella, which can otherwise hurt or even kill us. The law of unintended consequences may never have been more dramatically ratified.

I have made the case recently that religion and science need not be at odds, and that there are consequences when we act otherwise. Science makes a compelling case for our place in nature, and nature's place in us. So, too, does religion -- which attributes all creation to divine providence. Whichever view you favor, there seems abundant cause to respect the intricate web of life of which we are but one strand.

We are clearly deceiving ourselves to think we can untangle that web haphazardly, and not suffer consequences.


Dr. David L. Katz;

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