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Over the last few years I haven’t had much cause for complaint… Apart from one point where my stomach stopped operating like it usually did i.e. free of pain and without sporadic bouts of diarrhoea and vomiting. During these various episodes of malaise I had a deep and penetrating insight into how, not only should we be looking after our own bodies… But we should be looking after the planet that we call home too, as well as all the animals living on it… Especially those creatures (bacteria) living in our intestines and on our bodies.
As I’m sure any one who’s been ill knows, when one’s body goes through the stages of a fever/sickness, it seems to knock one’s mental (and physical) state of well being right out from the usual balanced groove of daily awareness. During a fever/sickness, one becomes almost dizzy and drunk on nausea, unable to focus on the usual things we like to get on with, such as work and play. Waves of sickness and pain rob us of our faculties and we find the only course of action is but to lie down and rest. Even when the fever/sickness finally wears off, it still takes at least a few days to get back into the usual rhythm of bodily awareness and feeling that we had before. Everything seems slow and we are aware of a dullness that still seems to linger on in our core.
Sickness is certainly not a pleasant state of being to find one’s “self” in… However, when it is over, I usually find my “self” exceptionally thankful that I am once again feeling “normal”. That slight derailment makes sure that I do not take for granted each and every moment of good health and well-being that I find my “self” enjoying. And I usually find myself wondering about the symptoms that this body presented (which I usually don’t care much about during the sickness). Funnily enough, every time I was ill, the same symptoms kept presenting themselves. We’re talking symptoms based around the stomach here: cramps, pains, diarrhoea, vomiting, etc… all of which literally left me so drained that I could hardly do anything other than lie down and rest/sleep through as much of it as I possibly could.
During one episode in particular, I remember – in a sort of very blurry way – that the pain in my stomach became so excruciating, it actually felt like someone had stabbed me in my belly and left me to writhe around on the floor dying slowly. Thankfully I have never been stabbed in the stomach before… But, if I had to take a wild guess at what it might actually feel like, I would say that what I had experienced on this one particular occasion wouldn’t be too far off the mark. To add to the pain I felt then, some other quite alarming symptoms had also begun to manifest, symptoms which I won’t mention here as I feel they probably go a bit beyond the mark of what should be reasonably be shared with most people on-line (I need a bit of privacy, regardless of sharing a lot of my inner most thoughts). Though I will mention that, while going through this particular ordeal, I began to feel the steady state of my mind loosing it’s usual calm and collected composure of being.
Somewhere over the course of that one evening, as the pain mounted steadily while driving back from the farm, when we arrived home, I literally began to scream at my partner to call me an ambulance. Just remembering that experience in my mind makes me flinch… Even 12 months on. I’ve literally broken bones before. Nothing to be proud of, I know… Rather I just felt like I could do some rather superhuman things when I was younger and get away without injury, like Superman might… And, for whatever the reason, I never really grasped the fact that I might have to consider suffering the consequences if something didn’t go according to plan (I put that down to reading far too many superhero comics). The most painful fracture I can remember was when I broke my arm in three places (elbow, wrist and scaphoid) while following my brother down a dry ski slope. What can I say… Plastic bristles laid over solid concrete isn’t exactly the most forgiving sort of surface media to ‘wipe-out’ on when travelling at 50 mph. And, yes, the pain was fairly full on for whole week after that particular accident. But the pain I felt in my stomach on that one occasion made that skiing fracture seem like a small paper cut or a bramble scratch.
During the onset of this illness, I acutely remember how my usual state of mental well being and general awareness (for my surroundings and the people in them) began to deteriorate into a rhythm of disturbed, knee-jerk reactions that echoed the pain I was in… I had literally become blasé about what I said to people around me, most of whom were only trying to help. At one point I clearly remember hurling insults at one of the nurses as she tried to find a vein from which to take a blood sample… Mind you, she had tried pricking my hand with a needle three times in a row but hadn’t found a suitable vein from which to get the blood she needed. After her third attempt I very curtly requested, in no uncertain terms, that she stop immediately and leave me alone… Which she did… But before she left, she insisted that it was imperative they took a blood sample in order to make an accurate diagnosis of my “unusual” symptoms. So off she went to find another nurse who might have better luck. When this new nurse appeared, nearly 15 minutes later, he pricked me another four times without any success. As you can imagine, my state of mind after the seventh “stab” had become irritable and mistrusting at beast… Not only was I in a bad way with the pain in my stomach, I was now also nursing a very bruised and painful left hand. Needless to say, with not a lot more they could do, they left me to rest alone in the emergency ward, simply giving me some pain-killers along with some tablets that were meant to treat stomach ulcers.
As I was lying there, I noticed my various bodily sensations… The first hour passed very slowly as the pain remained in full bloom, pulsing at times with that stabbing sharpness of a blade being twisted in my gut. However, a few hours later, as the exhaustion began to kick in from all the writhing over the last seven hours and the medication began to take effect, I must have fallen asleep. When I came to, I noticed that light was pouring in through the ward’s windows… By then the pain in my stomach had subsided to relatively manageable levels, while my swollen and sore hand was very heavily bruised. Mumbling thirstily for some water, the duty nurse came round to view me at about and asked how I was doing. I replied a lot better. She mentioned that, as they hadn’t been able to take a blood sample, they were obviously reluctant to offer a definitive diagnosis of what the episode I had endured could be. However, as they had noticed that the ulcer medication they had given me had seemed to reduce the pain a fair bit, they presumed it had probably been ulcer related (though she said that ulcers didn’t usually cause diarrhoea as well). As such, they prescribed me a course of tablets to take over a month to help reduce any persisting symptoms.
By this point, I had been ill with the same symptoms for nearly a whole year… And, regardless of all the blood tests and stool samples taken and given at the doctor’s each time, no one could figure out what was the matter. This culminating incident at AE was the first time I had been given any medication for my symptoms, something that hinted at what the my aliment might actually be. It’s hard being ill when one doesn’t know the cause of their symptoms. It wasn’t like I was drinking stagnant water from a contaminated well… Or even eating a dodgy India take-away… Rather these bouts of malaise usually came about without any warning whatsoever.
When I arrived home from the hospital later that morning by taxi – feeling a lot better than I had done the night before – I had a bit of shock. Walking through the front door, I immediately noticed that some of the banisters had been broken and were lying in pools of vomit, which were randomly splattered over much of the first floor landing. Other artefacts were also lying strewn across the floor, almost as though someone had ransacked the house looking for something. Looking at this mess before me, I slowly began to recall the events of the night before leading up to the ambulance arriving. Piece by piece the, and all quite vividly, I remembered how I had broken the banisters myself while in the grips of various painful spasms, in between which I had tossed books and anything else that came to hand on the ground as if to try to find some relief from the excruciating pain. To be fair, I never thought that anyone, let alone my “self”, would be able to do anything like that while in the grips of that much pain… But, somewhat shockingly, I realised that had forgotten my “self” during it all and thrown reason to the wind.
That particular episode, when set against the various other episodes that I had gone through over the previous few years (about 13 episodes in total, none of which were anywhere as near painful as this particular one), I was left wondering as to what it might be that was repeatedly causing these bouts of sporadic illness. Having gone to see my doctor at least seven times during this period, I had repeated to him the same symptoms with each new episode. However, he literally couldn’t figure it out. After all the various fecal tests and blood tests they had given me, nothing obvious showed up.
So without any clear reason for these episodes, and particularly bearing in mind my last experience in hospital, the doctor began to presume the worst. He recommended that I get a colonoscopy done as soon as possible as he thought my symptoms might be related to the onset of bowl cancer. When I heard this, I began to feel quite concerned and, as such, felt a bit depressed about the fact that I might well have to expect more illness to come. So I arranged pronto to have a colonoscopy done. Over a period of two months, while waiting for the results I fell ill a couple more times. Still, despite having had the colonoscopy, nothing untoward was revealed in my gut and colon, so the idea that these symptoms might relate to bowel cancer was ruled out.
Aside from this brief bit of relief, we were still nowhere nearer to discovering what the cause of these seemingly random bouts of stomach trouble were related to. Bearing in mind nothing nasty had been found in my stomach… And neither did I have any sign of stomach or bowel cancer… My doctor simply suggested that we wait until it happened again and, once the symptoms manifested again, we’d try to figure out what it might be.
This passive approach left me a bit startled, to say least… So I decided to take matters into my own hands. Thus, I began to read quite a bit about the stomach and how it functioned… In doing this, I found myself revisiting a lot of things that I had learnt during my university days. I was re-aquainted with the basic idea of how the stomach is populated with natural flora and fauna i.e. bacteria and fungi, that work and live in symbiosis with our bodies, helping us to digest the bulk of all the food that we eat, readily releasing the stored nutrients and energy within each morsel for our body to easily absorb… All the while taking what they needed for their own survival too. During this, one particular point that I kept bumping in to again and again (while reading through all various scientific papers) was about how most bacteria, if found in small enough numbers, were actually beneficial to the body… But if they grew disproportionately large in number, then they became pathogenic, causing infections and illness (which usually might not be diagnosed, because the bacteria found in one’s gut were expected to be there).
Pondering this point while ‘digesting’ several of articles recently published in the Scientific American, I revisited an idea that I had originally come across in one of my microbiology modules at university. The idea (derived from a fair amount of empirical research) demonstrated that minor changes in dietary habits i.e. increased consumption of refined sugars (which can specifically select for certain types of bacteria/fungi over others) and/or elevated ingestion of alcohol, can sometimes cause major imbalances between some of the natural gut flora and fauna that is usually found within our guts and, thus, give rise to stomach problems on one sort or another. This was thought to the major cause of that enigmatic condition that so many 21st century people seem to suffer from: Irritable Bowel Syndrome (or IBS for short). During that very lesson, it was also (somewhat obviously) stated that the intestinal ingestion of antibiotics (so as to treat various severe infections elsewhere within the body) can also cripple/impair the natural balance of bacteria within our stomachs and upon out bodies. It’s not rocket science… Put a strong broad spectrum antibiotic into a place where there are a broad and diverse range of bacteria and you’ll wipe a lot of them out. This obviously destroys the natural balance, leaving other bacteria that usually weren’t there to fill the gaps. For whatever the reason, only now are medical scientists and physicians starting to realise that the wide array of various stomach upsets (from IBS to diarrhoea) that commonly appear several years down the line might be due to people having been ‘blasted’ with antibiotic treatments.
Bearing in mind I had been prescribed quite a few antibiotics in my twenties and, in particular, once in my teens (where I almost died from a pneumococcal infection)… Not to mention I had also begun to enjoy a good bottle of fine French wine every now and again (as any microbiologist will tell you, alcohol is a good sterilising agent)… I began to wonder whether my own gut had fallen prey to an imbalance between the usual suspects of flora and fauna that normally helped me digest my food and lead a normal, healthy life style. So I very carefully started to recall all the various species of bacteria that I had learnt would be commonly found living in our guts… From Escherichia coli (various strains of which I worked with at university), Lactobacillus gasseri, Lactobacillu casei, Lactobacillu reuteri, Streptococcus thermophilus, Bacteroides thetaitaomicron and Helicobacter pylori, to name but a few microbes that commonly live in our guts, it became clear to me that we have a very varied selection of lodgers living within us… These lodgers – when living in harmoney with each other – pay their dues to themselves and us by creating the right harmony of chemicals and nutrients that directly result in our (both humans and bacteria) overall good health and well-being.
Besides these lodgers in our stomachs, we also have microbes living in our mouths and respiratory systems too e.g. Stretococcus viridans, Stretococcus salivarius, Neisseria sicca and Candida albicans (the yeast that causes “Thrush” infects). In fact, this thin film of microbial life doesn’t just exist inside our bodies… It also exists outside our bodies too. For example, on our skin we commonly find Staphylococcus haemolyticus, Staphylococcus epidermidis and Corynebacterium jeikeium… All of these bacteria usually live quite happily and peaceably in and amongst our body’s cellular activities. However, when our immune system is down or compromised in some way or another, some of these bacteria can break out in a rash (quite literally) of over population that in turn causes illness and malady in the patient. When these ‘riots’ break out, the usual course of action in severe cases would have been – as we saw used to happen in my twenties – to treat the patient and affected areas with antibiotics of one variety or another.
These broad-spectrum antibiotics would usually focus on a particular type of biochemical pathway that the culprit infectious organism would rely on to grow in numbers i.e. all penicillins are β-lactam antibiotics that are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms gram (gram positive or gram negative relates to the two main types of cell wall structure of bacterium in general). These antibiotic chemicals usually inhibit certain common biochemical mechanisms throughout a wide array of micro-organism, without any specificity to the particular aggravating organism… Thus, when these chemicals inhibit the biochemical pathways relating to the manufacture of cell walls, nearly every other type of bacteria that relied upon this common biochemical pathway to grown and increase in number would also be inhibited. As their life spans can be measured in days, nearly all of them would die off without any progeny to take their place. While this would solve the problem of the infection, it would also wreck the balance of other commensal bacteria that usually might have existed there too.
This mass genocide of microbial life in and on our bodies causes problems further down the line as, by upsetting the delicate balance that these organisms have established between themselves, when they grow back (and, believe me, they grown back because we find them everywhere in our environment, like when we shake hands with others, etc…) the balance is sometimes so different to what it used to be that big difference start to occur in the way they (some of them new strains of the same bacteria) operate and find balance between themselves. While we might not notice these changes immediately, within a few months, or even a few years, this new type of balance between microbial flora and fauna present in and within out bodies comes about to effecting us, sometimes beneficially or, at other times, not so beneficially.
Some people find it hard to believe that usually benign species micro-organisms can sometimes become unwitting pathogens as they grow beyond their usual numbers in order to fill a void left by another innocent victim of the doctor’s antibiotic ‘strike’. In fact, I was recently told by my doctor that antibiotics were not the only cause of imbalances in our gut’s ‘natural’ flora and fauna. Sometimes, modern diets of highly processed and overly sterilized foods leaves out various key ingredients that these bacteria need to survive. And nearly all processed foods now don’t have any key inoculations i.e. cultures of bacteria to re-introduce into our digestive systems, that would normally have been ingested through the regular (dare I say “normal”) diets of our ancestors a hundred years or so ago! In fact, modern food processing is essentially digesting the foods for us before hand into their basic chemical make ups and then packaging it. No bacteria are allowed to be present in the food, in case some of them are nasty ones… But this means that the bacteria living in our guts don’t have the usual nutrients needed for their own well being. As we have seen throughout various articles within this blog, balance is a BIG key factor to sustaining most complex systems.
Going back to remembering the experience of my 12 year old body being bombarded by a dual array of antibiotics to fend off a major infection that nearly took my life… I can’t say that I ever really felt the same after that treatment. It was no way like any of the other brief antibiotic runs that I had been given to overcome colds and stomach problems, etc… The feeling I had been left with was harsher, almost cleaner, than before… As though something integral to my “life force” had been taken away. Over the years I began to get used to this new feeling in my body. While I could feel something had changed (though I had no idea exactly what), I was better than I had been, so I didn’t feel that I needed to ask too many questions. Saying that, whenever I became ill after that blitz, it was usually related – in one way or another – to my stomach and bowels. So, while focusing on my innards during this painful fever, I began thinking about which bacteria I could and should try to reintroduce into my gut in order to help create a healthy balance of flora and fauna… After which, more importantly, I began to wonder where these bacteria came from originally… ?
As I thought this through – perceiving the direct line of contact between my body and its environment from birth through to present – it dawned on me that as soon as we are born, bacteria move in to stake their claim in our digestive and respiratory tracts, as well as around our teeth and on our skin and various orifices. Would you believe that the first wave of these colonising organisms probably comes directly from our mothers: when we come out of their vaginal passage, we are coated in a sticky mess of amniotic fluids and placenta… Just as in our mother’s urinary tract (and our father’s too) there are known to be similar microbes that live within our passages. It was like a game of tag. These microbes would easily rub off on our own naked form as the rough and heavy pushing of our mothers to dislodge our tiny bodies from their wombs pushed us along the length of their vaginas and into the cold light of day. The next wave of colonizers would probably come from the foods we ingested… No doubt, as we are breast fed, we pick up bacteria from our mother’s skin and from her milk. Then, as these organisms grow inside and upon us, they establish increasingly more and more complex communities, like a forest that gradually takes over a clearing. By the time we’re a few years old, these communities have matured (ever notice the way babies changes in smell?), and we carry them with us, more or less, for our entire lives.
Thinking about how readily bacteria go through thousands of generations in just a few days (for perspective, it takes humans tens of thousands of years to do that), the rate at which they evolve and adapt to their surroundings is astonishing. Sometimes the bacteria within our guts can become some in tune with the chemicals secreted by other organisms that they evolve into fitting into a highly delicate and specific niche, tailored specifically for our own bodies and diets. Remove one of those organisms from that complex dynamic, and change ripples through the system. Even if you replace it with another bacteria of exactly the same species as before, because the new bacteria have gone through the naturally selective pressures from the environmental chemical soup found in our guts, they don’t fit exactly in that niche like the other bacterial organism might have done. Any change in our gut usually causes some sort of feeling or upset on our part. So we have to look them if we want to avoid pain and discomfort.
I still find it amazing that our bodies harbour 100 trillion bacterial cells, which outnumbers our own bodily human cells 10 to 1!!! It’s easy to overlook this astonishing fact… Especially, if you had no idea about the workings and goings on within the complex biochemical ecosystem that we call our bodies. Bacteria are tiny in comparison to human cells; they contribute just a few pounds to our weight and remain totally invisible to our naked eyes. As such, it’s little wonder that science has (until late) overlooked the major roles that they play in helping us and our bodies remain healthy and active.
Researchers have usually largely concerned themselves only with the negative roles that “some” bacteria play as pathogens: the devastating effects of a handful of infectious organisms have always seemed more urgent than what has been considered a benign and relatively unimportant relationship with “good” bacteria. Because of this somewhat backward view, it is little wonder why I was where I was i.e. suffering from gross bouts of malaise, including sickness and diarrhoea, with regular occurence. However, since I have begun caring for these little “friends” of mine living in my intestine, eating a diverse selection of foods that feed and help them grow and remain comfortable (as well as eating food that sometimes has quite of few them already growing in), I have found that I have not had ANY cause for complaint. As such, this new awareness of my relative “self” and the body that it relates to, as well as the “friendly” microscopic inhabitants living on it, has meant that I can now properly look after it all… Properly understanding my “self” has opened the door to helping those who were complaining to me about the slightly unbalanced diet that I was feeding upon.
Now, all satisfied, I am happy to report that “they” feel happy too. I know this because my gut, which – would you believe – is an extension of my brain, feels happy. This bacterial hub of a body – that teems with trillions of microbes, all of whom make my life easier to live by digesting a lot of the foods I eat into natural and easily assimilable chemicals to keep me healthy and in balanced awareness – feels happy. In fact, bearing in mind my Buddhist tendencies, I have to say I feel that they are now happy to eat at the same table as I do.
In many ways, I find this research into how to look after my passengers within me – ones that out number my own cells and help me to live a happy and carefree life of balanced biochemical awareness – is a powerful analogy for understanding interdependence and our relationship with this planet. Without all the help of these bacteria i.e. their respective participation in my body’s biochemical needs, my life is one of illness and malaise. However, if I take the time to care for them and properly look after them, then they happily support me and keep me functioning in the usual groove of good health (something that I now never take for granted any more). Amazing really. No idea why a doctor couldn’t have told me that in the first place. !?
Much in the same way, our planet needs us to look after it so it can support us happily. Without all these organisms living on it – and without our care and help (whether bees or other insects to do the pollinating OR trees to replenish our air), we will not be able to live here in the same ease and comfort that we seem to enjoy at present. We need to continually check ourselves and understand that we should never take for granted all the wonders of life around us. We are just as much a part of them as they are a part of us. When we realise this, we will see how far away from a healthy and sustainable way of life we are here in Earth. Only then will we have the ability to properly do something about it.
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How Bacteria In Our Bodies Protect Our Health
Researchers who study the friendly bacteria that live inside all of us are starting to sort out who is in charge—microbes or people? Biologists once thought that human beings were physiological islands, entirely capable of regulating their own internal workings. Our bodies made all the enzymes needed for breaking down food and using its nutrients to power and repair our tissues and organs. Signals from our own tissues dictated body states such as hunger or satiety. The specialized cells of our immune system taught themselves how to recognize and attack dangerous microbes—pathogens—while at the same time sparing our own tissues.
Over the past 10 years or so, however, researchers have demonstrated that the human body is not such a neatly self-sufficient island after all. It is more like a complex ecosystem—a social network—containing trillions of bacteria and other micro-organisms that inhabit our skin, genital areas, mouth and especially intestines. In fact, most of the cells in the human body are not human at all. Bacterial cells in the human body outnumber human cells 10 to one. Moreover, this mixed community of microbial cells and the genes they contain, collectively known as the microbiome, does not threaten us but offers vital help with basic physiological processes—from digestion to growth to self-defence.
So much for human autonomy.
Biologists have made good progress characterizing the most prevalent species of microbes in the body. More recently, they have begun to identify the specific effects of these residents. In so doing, they are gaining a new view of how our bodies function and why certain modern diseases, such as obesity and autoimmune disorders, are on the rise.
Out Of Many, One
When people think of microbes in the body, they usually think of pathogens. Indeed, for a long time researchers focused solely on these harmful bugs and ignored the possible importance of more benign ones. The reason, argues biologist Sarkis K. Mazmanian of the California Institute of Technology, is our skewed view of the world. “Our narcissism held us back; we tended to think we had all the functions required for our health,” he says. “But just because microbes are foreign, just because we acquire them throughout life, doesn’t mean they’re any less a fundamental part of us.”
Indeed, all humans have a microbiome from very early in life, even though they do not start out with one. Each individual acquires his or her own community of commensals (from the Latin for “sharing a table”) from the surrounding environment. Because the womb does not normally contain bacteria, newborns begin life as sterile, singular beings. But as they pass through the birth canal, they pick up some of Mom’s commensal cells, which then begin to multiply. Breastfeeding and handling by proud parents, grandparents, siblings, and friends—not to mention ordinary contact with bedsheets, blankets, and even pets—quickly contribute to an expanding ark of microbes. By late infancy our bodies support one of the most complex microbial ecosystems on the planet.
For the past five years or so scientists have been working to characterize the nature of this ecosystem. The task has been devilishly difficult. The bacterial cells in the intestines, for example, have evolved to grow in the crowded, oxygen-free environment of the gut, so many species do not survive well in the lonely expanse of a petri dish. Researchers have gotten around this problem, however, by studying the genetic instructions, the strands of DNA and RNA, found within a microbe rather than the whole cell itself. Because DNA and RNA can be manipulated in a normal, oxygenated laboratory environment, investigators can take microbial samples from the body, extract the genomic material and analyze the results.
Each species of commensal bacteria has a signature, it turns out—its own unique version of a gene (known as the 16S ribosomal RNA gene) that codes for a particular RNA molecule found in the ribosomes, the protein-making machinery of cells. By determining the sequence of this gene, scientists are creating a catalogue of the entire human microbiome. In this way, they can glean which species exist in our bodies and how the precise combination of species may differ from one person to another.
The next step is to analyze other genes found in the microbial community to determine which ones are active in people and what functions they perform. Again, that chore is a tall order because of the great number of species and because their genes get mixed together in the extraction process. Determining whether a specific bacterial gene is active (or expressed) in the body is relatively straightforward; figuring out to which species that particular gene belongs is not. Fortunately, the development of ever more powerful computers and ultrafast gene sequencers in the first decade of the 21st century has turned what would once have been an impossible task of sorting and analysis into merely a very complicated one.
Two separate groups of scientists, one in the U.S. and the other in Europe, have harnessed this new technology to enumerate the bacterial genes within the human body. In early 2010 the European group published its census of microbial genes in the human digestive system—3.3 million genes (from more than 1,000 species)—about 150 times the 20,000 to 25,000 genes in the human genome.
Research into the nature of the human microbiome has yielded many surprises: no two people share the same microbial makeup, for instance—even identical twins. This finding may help unravel a mystery presented by the Human Genome Project, which confirmed that the human DNA of all people the world over is 99.9 percent alike. Our individual fates, health and perhaps even some of our actions may have much more to do with the variation in the genes found in our microbiome than in our own genes. And although the microbiomes of different people vary markedly in the relative number and types of species they contain, most people share a core complement of helpful bacterial genes, which may derive from different species. Even the most beneficial bacteria can cause serious illness, however, if they wind up somewhere they are not supposed to be—for example, in the blood (causing sepsis) or in the web of tissue between the abdominal organs (causing peritonitis).
Friends With Benefits
The first inkling that beneficial bugs might do us good came decades ago during research on digestion and the production of vitamins in the guts of animals. By the 1980s investigators had learned that human tissue needs vitamin B12 for, among other things, cellular energy production, DNA synthesis and the manufacture of fatty acids and had determined that only bacteria synthesize the enzymes needed to make the vitamin from scratch. Similarly, scientists have known for years that gut bacteria break down certain components of food that would otherwise be indigestible and would pass out of the body unused. Only in the past few years, however, have they learned the juicy details: two commensal species in particular play major roles in both digestion and the regulation of appetite.
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Perhaps the prime example of a helpful bug sounds like it was named after a Greek sorority or fraternity. Bacteroides thetaiotaomicron is a champion carbohydrate chomper, capable of breaking down the large, complex carbohydrates found in many plant foods into glucose and other small, simple, easily digestible sugars. The human genome lacks most of the genes required to make the enzymes that degrade these complex carbohydrates. B. thetaiotaomicron, on the other hand, has genes that code for more than 260 enzymes capable of digesting plant matter, thus providing humans with a way to efficiently extract nutrients from oranges, apples, potatoes and wheat germ, among other foods.
Fascinating details about how B. thetaiotaomicron interacts with, and provides sustenance to, its hosts come from studies of mice raised in a completely sterile environment (so they had no microbiome) and then exposed only to this particular strain of microbes. In 2005 researchers at Washington University in St. Louis reported that B. thetaiotaomicron survives by consuming complex carbohydrates known as polysaccharides. The bacteria ferment these substances, generating short-chain fatty acids (essentially their feces) that the mice can use as fuel. In this way, bacteria salvage calories from normally indigestible forms of carbohydrate, such as the dietary fiber in oat bran. (Indeed, rodents that are completely devoid of bacteria have to eat 30 per cent more calories than do rodents with an intact microbiome to gain the same amount of weight.)
The study of the microbiome has even partially rehabilitated the reputation of one disease-causing bacterium called Helicobacter pylori. Fingered by Australian physicians Barry Marshall and Robin Warren in the 1980s as the causative agent of peptic ulcers, H. pylori is one of the few bacteria that seem to thrive in the acidic environment of the stomach. While continued use of medicines known as nonsteroidal anti-inflammatory drugs, or NSAIDs, had long been known to be a common cause of peptic ulcers, the finding that bacteria contributed to the condition was remarkable news. After Marshall’s discovery, it became standard practice to treat peptic ulcers with antibiotics. As a result, the rate of H. pylori–induced ulcers has dropped by more than 50 percent.
Yet the matter is not so simple, says Martin Blaser, now a professor of internal medicine and microbiology at New York University who has studied H. pylori for the past 25 years. “Like everyone, I started working on H. pylori as a simple pathogen,” he says. “It took a few years for me to realize that it was actually a commensal.” In 1998 Blaser and his colleagues published a study showing that in most people, H. pylori benefits the body by helping to regulate levels of stomach acids, thus creating an environment that suits itself and its host. If the stomach churns out too much acid for the bacteria to thrive, for example, strains of the bug that contain a gene called cagA start producing proteins that signal the stomach to tone down the flow of acid. In susceptible people, however, cagA has an unwelcome side effect: provoking the ulcers that earned H. pylori its nasty rap.
A decade later Blaser published a study suggesting that H. pylori has another job besides regulating acid. For years scientists have known that the stomach produces two hormones involved in appetite: ghrelin, which tells the brain that the body needs to eat, and leptin, which—among other things—signals that the stomach is full and no more food is needed. “When you wake up in the morning and you’re hungry, it’s because your ghrelin levels are high,” Blaser says. “The hormone is telling you to eat. After you eat breakfast, ghrelin goes down,” which scientists refer to as a postprandial (from the Latin word prandium, for “a meal”) decrease.
In a study published last year, Blaser and his colleagues looked at what happens to ghrelin levels before and after meals in people with and without H. pylori. The results were clear: “When you have H. pylori, you have a postprandial decrease in ghrelin. When you eradicate H. pylori, you lose that,” he says. “What that means, a priori, is that H. pylori is involved in regulating ghrelin”—and thus appetite. How it does so is still largely a mystery. The study of 92 veterans showed that those treated with antibiotics to eliminate H. pylori gained more weight in comparison to their uninfected peers—possibly because their ghrelin level stayed elevated when it should have dropped, causing them to feel hungry longer and to eat too much.
Two or three generations ago more than 80 percent of Americans played host to the hardy bug. Now less than 6 percent of American children test positive for it. “We have a whole generation of children who are growing up without H. pylori to regulate their gastric ghrelin,” Blaser says. Moreover, children who are repeatedly exposed to high doses of antibiotics are likely experiencing other changes in their microbial makeup. By the age of 15, most children in the U.S. have had multiple rounds of antibiotic treatment for a single ailment—otitis media, or ear infection. Blaser speculates that this widespread treatment of young children with antibiotics has caused alterations in the compositions of their intestinal microbiome and that this change may help explain rising levels of childhood obesity. He believes that the various bacteria within the microbiome may influence whether a certain class of the body’s stem cells, which are relatively unspecialized, differentiate into fat, muscle or bone. Giving antibiotics so early in life and thereby eliminating certain microbial species, he argues, interferes with normal signaling, thereby causing overproduction of fat cells.
Could the accelerating loss of H. pylori and other bacteria from the human microbiome, along with societal trends—such as the easy availability of high-calorie food and the continuing decline in manual labor be enough to tip the balance in favor of a global obesity epidemic? “We don’t know yet whether it’s going to be a major or minor part of the obesity story, ” he says, “but I’m betting it’s not trivial.”
The widespread use of antibiotics is not the only culprit in the unprecedented disruption of the human microbiome in Blaser’s view. Major changes in human ecology over the past century have contributed as well. The dramatic increase in the past few decades in the number of deliveries by cesarean section obviously limits the transfer through the birth canal of those all-important strains from Mom. (In the U.S., more than 30 percent of all newborns are delivered by C-section, and in China—land of one child per couple—the operation is responsible for nearly two thirds of all births to women living in urban areas.) Smaller family sizes throughout the world mean fewer siblings, who are a prime source of microbial material to their younger siblings during early childhood years. Even cleaner water—which has saved the lives of untold millions—exacts a toll on the human microbiome, reducing the variety of bacteria to which we are exposed. The result: more and more people are born into and grow up in an increasingly impoverished microbial world.
A Delicate Balance
As the ongoing studies of B. thetaiotaomicron and H. pylori illustrate, even the most basic questions about what these bacterial species are doing in the body lead to complicated answers. Going one step further and asking how the body responds to the presence of all these foreign cells in its midst introduces even greater complexity. For one thing, the traditional understanding of how the immune system distinguishes the body’s own cells (self) from genetically different cells (nonself) suggests that our molecular defenses should be in a constant state of war against these myriad interlopers. Why the intestines, for example, are not the scene of more pitched battles between human immune cells and the trillions of bacteria present is one of the great, as yet unsolved mysteries of immunology.
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The few clues that exist offer tantalizing insights into the balancing act between the microbiome and human immune cells that has taken some 200,000 years to calibrate. Over the eons the immune system has evolved numerous checks and balances that generally prevent it from becoming either too aggressive (and attacking its own tissue) or too lax (and failing to recognize dangerous pathogens). For example, T cells play a major role in recognizing and attacking microbial invaders of the body, as well as unleashing the characteristic swelling, redness and rising temperature of a generalized inflammatory response to infection by a pathogen. But soon after the body ramps up its production of T cells, it also starts producing so-called regulatory T cells, whose principal function seems to be to counteract the activity of the other, pro-inflammatory T cells.
Normally the regulatory T cells swing into action before the pro-inflammatory T cells get too carried away. “The problem is that many of the mechanisms that these proinflammatory T cells use to fight infection—for example, the release of toxic compounds—end up blasting our own tissues,” says Caltech’s Mazmanian. Fortunately, the regulatory T cells produce a protein that restrains the proinflammatory T cells. The net effect is to tamp down inflammation and prevent the immune system from attacking the body’s own cells and tissues. As long as there is a good balance between belligerent T cells and more tolerant regulatory T cells, the body remains in good health.
For years researchers assumed that this system of checks and balances was generated entirely by the immune system. But in yet another example of how little we control our own fate, Mazmanian and others are starting to show that a healthy, mature immune system depends on the constant intervention of beneficial bacteria. “It goes against dogma to think that bacteria would make our immune systems function better,” he says. “But the picture is getting very clear: the driving force behind the features of the immune system are commensals.”
Mazmanian and his team at Caltech have discovered that a common microorganism called Bacteroides fragilis, which lives in some 70 to 80 percent of people, helps to keep the immune system in balance by boosting its anti-inflammatory arm. Their research began with observations that germ-free mice have defective immune systems, with diminished function of regulatory T cells. When the researchers introduced B. fragilis to the mice, the balance between the pro-inflammatory and anti-inflammatory T cells was restored, and the rodents’ immune systems functioned normally.
But how? In the early 1990s researchers started characterizing several sugar molecules that protrude from the surface of B. fragilis—and by which the immune system recognizes its presence. In 2005 Mazmanian and his colleagues showed that one of these molecules, known as polysaccharide A, promotes maturation of the immune system. Subsequently, his laboratory revealed that polysaccharide A signals the immune system to make more regulatory T cells, which in turn tell the pro-inflammatory T cells to leave the bacterium alone. Strains of B. fragilis that lack polysaccharide A simply do not survive in the mucosal lining of the gut, where immune cells attack the microbe as if it were a pathogen.
In 2011 Mazmanian and his colleagues published a study in Science detailing the full molecular pathway that produces this effect—the first such illumination of a molecular pathway for mutualism between microbe and mammal. “B. fragilis provides us with a profoundly beneficial effect that our own DNA for some reason doesn’t provide,” Mazmanian says. “In many ways, it co-opts our immune system—hijacks it.” Unlike pathogens, however, this hijacking does not inhibit or reduce our immune system performance but rather helps it to function. Other organisms may have similar effects on the immune system, he notes: “This is just the first example. There are, no doubt, many more to come.”
Alas, because of lifestyle changes over the past century, B. fragilis, like H. pylori, is disappearing. “What we’ve done as a society over a short period is completely change our association with the microbial world,” Mazmanian says. “In our efforts to distance ourselves from disease-causing infectious agents, we have probably also changed our associations with beneficial organisms. Our intentions are good, but there’s a price to pay.”
In the case of B. fragilis, the price may be a significant increase in the number of autoimmune disorders. Without polysaccharide A signaling the immune system to churn out more regulatory T cells, the belligerent T cells begin attacking everything in sight—including the body’s own tissues. Mazmanian contends that the recent sevenfold to eightfold increase in rates of autoimmune disorders such as Crohn’s disease, type 1 diabetes and multiple sclerosis is related to the decline in beneficial microbes. “All these diseases have both a genetic component and an environmental component,” Mazmanian says. “I believe that the environmental component is microbiotic and that the changes are affecting our immune system.” The microbial shift that comes with changes in how we live—including a decrease in B. fragilis and other anti-inflammatory microbes—results in the underdevelopment of regulatory T cells. In people who have a genetic susceptibility, this deviation may lead to autoimmunity and other disorders. Or at least that is the hypothesis. At this stage in the research, the correlations in humans between lower microbial infections and increased rates of immune disease are only that—correlations. Just as with the obesity issue, teasing apart cause and effect can be difficult. Either the loss of humanity’s indigenous bugs have forced rates of autoimmune diseases and obesity to shoot up or the increasing levels of autoimmunity and obesity have created an unfavorable climate for these native bugs. Mazmanian is convinced that the former is true—that changes in the intestinal microbiome are contributing significantly to rising rates of immune disorders. Yet “the burden of proof is on us, the scientists, to take these correlations and prove that there is cause and effect by deciphering the mechanisms underlying them,” Mazmanian says. “That is the future of our work.”
By Jennifer Ackerman
More to Explore:
Who Are We? Indigenous Microbes and the Ecology of Human Diseases. Martin J. Blaster in EMBO Reports, Vol. 7, No. 10, pages 956–960; October 2006. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618379
A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing. Junjie Qin et al. in Nature, Vol. 464, pages 59–65; March 4, 2010.
Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System? Yun Kyung Lee and Sarkis K. Mazmanian in Science, Vol. 330, pages 1768–1773; December 24, 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159383
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If you’d like to find out where I originally sourced this Scientific American articles from, please click here.
