The Benefits of Bacteria

We have been killing bacteria which make us sick, but what if they have also been keeping us alive? This is the question raised in an article in the New Yorker (October, 2012) entitled “Germs are Us” by Michael Specter, a respected journalist who writes mainly on science and global public health. In 1982 two scientists, Barry Marshall and J. Robin Warren, made the surprising discovery that the main cause of gastric ulcers was the bacterium, Helicobacter pylori (or H. pylori for short).  Previously stress had been thought to be the main cause of this condition, but now it turned out that it could be successfully treated by a combination of two antiobiotics plus a protein pump inhibitor (PPI). For this discovery Marshall and Warren received the Nobel Prize for medicine in 2005. This seemed to confirm the widely held view that bacteria are “bad” and need to be destroyed.

In a paper in the British Medical Journal in 1998, Martin J. Blaser, the chairman of the Department of Medicine and a professor of microbiology at the New York University School of Medicine, raised doubts about the attempt to eliminate H. pylori completely from all patients. He argued that there was little evidence that this was justified and pointed out that no one seemed to have considered what the consequences of doing this might be. He wondered how an ancestral component of humanity could have survived for so long if it only caused harm to humans. He notes that studies of primates and humans in developing countries suggest that before 1800 nearly all humans carried H. pylori or closely related bacteria in their stomachs. Since then there has been a decline in the prevalence of H. pylori, perhaps because of improved diet and hygiene, or because most transmission is from child to child and families have become smaller. However its prevalence up to this time makes it seem reasonable to regard H. pylori as part of the normal bacterial flora which we acquire in the first few months of life.

With this drop in H. pylori colonization there has been a steady increase in the incidence of adenocarcinoma of the cardia, or proximal part of the stomach, and of the distal oesophagus. Although further studies are required to demonstrate a causal connection, rather than a mere chance association, between the increase in these once rare forms of cancer and the drop in H. pylori colonization, it seems likely, in the absence of any other plausible explanations, that H.pylori may well have been a protective factor against the development of these types of cancer. “Germs make us sick, but everyone focuses on the harm. And it’s not that simple, because without most of these organisms we could never survive”, Blaser told the New Yorker.

Our thinking about disease has been dominated in recent years by possible genetic causes, ever since the discovery of the structure and function of DNA as the genetic code which manufactures proteins that in turn build the fundamental components of the body. Of course genes are very important but so are bacteria too. Blaser makes the point that damage to DNA or faulty interactions between genes cannot by itself explain how rapidly the incidence of many diseases, such as gastric and oesophageal adenocarcinoma, has risen.

But bacteria play an important role not only in the incidence of diseases but also in the maintenance of our health. We first come into contact with bacteria as we pass through our mother’s birth canal. By the time a child begins to crawl it is surrounded by an invisible cloud of a hundred trillion or more micro-organisms, known as a microbiome or biome, made up not only of bacteria, but of viruses and fungi as well. Each species has its distinctive biome: alligators, dogs, cats and dolphins all have their own biomes. In 2007 the US National Institute of Health began the Human Microbiome Project to identify the micro-organisms that make up our biome and study how they interact when we are ill. David A. Relman, a professor of medicine, microbiology and immunology at Stanford University school of Medicine, is quoted as saying, “We have to stop looking at medicine as a war between invading pathogens and our bodies. This sort of stewardship has more in common with park management than it does with our current practice of trying, in the broadest possible way, to kill microbes”. Specter notes: “Medicine becomes a matter of cultivation, as if our bacterial cells were crops in a field”.

Evidence that bacteria help as well as harm us is growing. In 2012 Susan Lynch, an associate professor of medicine at the University of California at San Francisco and her co-workers reported that the bacterium Lactobacillus sakei seems to protect us against sinusitis and that people who have this microbe have a far lower incidence of this condition. Ilseung Chung of the New York University School of Medicine, published a study in 2012 showing that antibiotics which destroyed bacteria commonly found in the gastro-intestinal tract of mice, impaired the ability of these mice to metabolize food efficiently with the consequence that they absorbed more calories more quickly and became obese.
Just as herbicides, used the wrong way, can kill plants we need for food as well as weeds, so too can antibiotics adversely alter our microbiome and make us more susceptible to certain diseases. Of course, the development of antibiotics is one of the major causes of the dramatic increase in life expectancy in many countries over the last seventy years. But, to quote Blaser again, “Whenever they are used, though, there is collateral damage. And we are only now fully learning how severe that damage has been.” The “collateral damage” here is not only the increase in the incidence of some diseases, but also the development of resistant strains of bacteria through the excessive use of antibiotics. This is happening in the case of H.pylori, where resistance to two of the widely used antibiotics, metronidazole and clarithromycin, has been increasing, thus making it necessary to treat infection with a combination of two, or even three, antibiotics. An important point here is that not only medical staff, but also patients need to be educated about the dangers of antibiotics. Many patients suffering from the common cold, for instance, put pressure on doctors to prescribe antibiotics, although these are ineffective in this case, as the common cold is a viral, not a bacterial infection.

H. pylori is probably the best understood of the bacteria of the human microbiome. Whether it is dangerous or beneficial depends on the human ecosystem in which it is to be found. In 2007 Blaser and Chen found that people who did not have H. pylori in their gastrointestinal tract were more likely to have had asthma as children. In 2011 Anne Muller at the Institute of Molecular Cancer Research at the University of Zurich infected half of a cohort of mice with various allergens and found that those without the bacterium got asthma whereas those with the bacterium did not.

One hope for the future is that bacteria can be used prophylactically and perhaps even therapeutically. Blaser told the New Yorker: “We will need to make sure that pregnant women have the appropriate microbial communities to pass on to their children. If they don’t we will have to give them to the kids after they are born. Then, for certain bacteria, like Helicobacter, at the age of thirty or forty, they could go to a clinic and have them eradicated. That way people can get the benefit of these organisms in early life without having to pay the cost as they age.” The “cost” in this case is the increased risk of childhood asthma.

Paul Crichton
24 December 2012


References

Martin Specter, Germs are Us, New Yorker, Oct 22, 2012
Martin J Blaser, Helicobacter pylori and gastric diseases. BMJ, 1998;316:1507