Bugs are just as important as our own genome. Ninety-nine percent of all active genes in the body are not human. We have about a hundred trillion bacteria in the gut. Bacteria are a group of microorganisms which lack a nuclear membrane and have a cell wall of unique disposition. Most bacteria are unicellular. Bacteria are widely distributed in the soil, water and air; parasitic bacteria live in humans, animals and plants. Sometimes bacteria cause diseases by producing poisons and toxins. Bacterial infections can be treated with antibiotics and other bactericides. The most common bacterial infections are meningitis, sinusitis, bronchitis, pneumonia, salmonella and tetanus.
Biological chemist JEREMY NICHOLSON brings a fresh perspective to the study of disease. He looks at the body as a miniature ecosystem in which disorders as different as obesity, allergies, and even autism relate to the landscape of microbes living within our guts. Our idiosyncratic responses to drugs and diseases might have as much to do with organisms such as Helicobacter pylori and Clostridium difficile as with our own DMA. In order to treat many complex diseases, therefore, we may have to start dealing with the genes of the trillions of bacteria inside us. Nicholson and his research team at Imperial College London are currently decoding how these microscopic bugs communicate with us. Someday doctors may use his findings to pinpoint which drugs will interact most effectively with each patient's personal ecology.
Why do you think microbes are so important to understanding human health?
Bugs are just as important as our own genome. Ninety-nine percent of all active genes in the body are not human. We have something like 1.5 to 2 kilograms [about 4 pounds] of bacteria inside, and a hundred trillion bacteria in the gut. We've only recently discovered how important they are in many aspects of our lives. I'm trying to understand why some people have good and bad responses to drugs, depending on the bugs in their bodies, and how we can reengineer biology to change the way bugs work on drugs.
How do all the microbes that normally inhabit our bodies affect us?
They are important to a whole range of etiologies and pathogenesis of different diseases, including type 1 diabetes and obesity. To improve medicine in the future, we must understand how to regulate the bugs, control them, and learn the language they use to communicate with us. It is a fundamental biology problem. Bugs might be a unifying factor that connects what seem to be very different illnesses that may actually have common etiologies. In addition to diabetes and obesity, colonic cancers, gut inflammatory conditions, and most likely many autoimmune disorders and allergies have underlying gut microbial development problems. These diseases all look different, but the root cause is unfavorable immunity and abnormal bug interactions.
How do we get these colonies of bugs? Are we born with them?
You get your first bugs from your mother at birth, if it's a normal birth. If it's a cesarean, you do not get them from your mother [but get them quickly from the environment]. So there is a sort of virtual heritability of the microorganisms that you get. But your microbes then develop during your life, and according to your early exposures to different diets and stressors and things like that, your ecology will change.
How will your research alter the way we develop and take drugs?
Most drugs don't work for most people. For many diseases, you have to go through a range of therapies before you find the right one. Some adverse reactions are genetic, but other times they're probably related to the interaction between your bugs and your own genome. Drug companies developing new therapies don't look at the bugs—and they're an incredibly important component of the system. Several major pharmaceutical companies are starting to get interested in this area, and a few papers are coming out soon that are going to give them a bit of a rocket, because they're going to realize how important bugs are.
Should we worry about the growth in antibiotic use, then? Antibiotics selectively kill bugs. Some bugs are more resistant or tougher than others. Whenever you take an antibiotic you kill some bacteria, but others will take over. If the populations and ecology change permanently, which they might do, then you have changed your biology, because you've changed your symbiotic associations. If an infant has an earache and you give it Antibiotics, you are introducing a huge new selection pressure in the biology, which might just change the course of the ecological development in the gut, which might, years later, have other biological consequences and change the disease risks. When we take Antibiotics, we reselect the microflora in our guts. I'm not just talking about making pathogens antibiotic-resistant. That's what people worry about, but we're actually reselecting an ecology that we've evolved with, which will have unforeseen consequences in human biology.
What are the practical implications of your research?
The main point is this: The human body is a symbiotic mixture of many genomes that interact in space and time. A disease affects all components of the system, and we can best advance therapies for many complex disease traits by considering the human and bug ge-nomic components. Doctors could look at the community of bugs living in a person to determine risk and diagnosis by genetically screening the bugs with chip technology or by doing metabolic profiling to measure bug metabolites.
What do these findings mean for the future of medical treatment?
You've got to look at big biology in all its glory and complexity—a full systems biology, where the system is all the genes, proteins, metabolites, cells, and external organisms that interact with those in the gut. That is the total system that is the human body, and that's the thing that has to be grasped in the future if we're going to understand personalized health care, and why so many diseases are changing in the population so rapidly, and why everyone's getting fatter, for instance. All of that connects to bugs.
Interview by Amy Barth from Discover magazine (Summer 2009).
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Doxycycline Doxycyline and alcohol:
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Alcohol and Antidepressants:
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Gentamicin Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative bacteria. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin found in certain gram negative organisms).
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Zithromax Zithromax, Sumamed (generic name: azithromycin) is a semi-synthetic macrolide antibiotic chemically related to erythromycin and clarithromycin (Biaxin). It is effective against a wide variety of bacteria organisms, such as Hemophilus influenzae, Streptococcus pneumoniae, Mycoplasma pneumoniae, Staphylococcus aureus, and mycobacterium avium, and many others. It is unusual in that it stays in the body for quite a while, allowing for once a day dosing and for shorter treatment courses for most infections. Azithromycin, like all macrolide antibiotics, prevents bacteria from growing by interfering with their ability to make proteins. Due to the differences in the way proteins are made in bacteria and humans, the macrolide antibiotics do not interfere with humans' ability to make proteins.
Zovirax Oral acyclovir is used to treat initial genital herpes infections and to treat patients with recurrent (6 episodes per year) severe genital herpes.
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Bugs are just as important as our own genome. Ninety-nine percent of all active genes in the body are not human. We have about a hundred trillion bacteria in the gut. Bacteria are a group of microorganisms which lack a nuclear membrane and have a cell wall of unique disposition. Most bacteria are unicellular. Bacteria are widely distributed in the soil, water and air; parasitic bacteria live in humans, animals and plants. Sometimes bacteria cause diseases by producing poisons and toxins. Bacterial infections can be treated with antibiotics and other bactericides. The most common bacterial infections are meningitis, sinusitis, bronchitis, pneumonia, salmonella and tetanus.
How do all the microbes that normally inhabit our bodies affect us?
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