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YOU are home to 10,000 species of bacteria. The vast majority, more than 99 per cent, cause you no harm. Indeed, many actually help by providing you with nutrients, tuning your immune system, balancing your metabolism and warding off mood disorders. You depend on these bugs.

Yet as anyone who鈥檚 had an upset stomach after taking antibiotics can attest, when we target the dangerous minority of disease-causing species, we often wind up killing off the good ones too. Now, after generations of doctors prescribing antibiotics for every sniffle, we know that the collateral damage goes well beyond the occasional tummy ache.

Indiscriminately wiping out bacteria may be contributing to rising levels of asthma, allergies, obesity and many more conditions. These effects, together with the growing threat from antibiotic resistance, have some researchers advocating a sea change in the battle against the bugs: after 70 years of fighting to wipe them out, it may be time for a truce. If we can disarm harmful bacteria without killing them, we may be able to reduce antibiotic resistance, take the strain off these overworked drugs and leave our helpful inhabitants be. Doing so may even mean resurrecting some forgotten strategies from the past. If the 20th century was defined by our ability to kill off deadly bugs, then the 21st will be known as the era in which we learned to get along.

In the latter part of the 19th century, strong evidence that germs cause disease kicked off more than a century of war against bacteria. We expunged them from our water, food and homes with disinfectants; roused our immune systems against them with vaccines and wiped them out with penicillin and other chemical weapons. Human deaths caused by infectious diseases , contributing to a broader transformation of society. We take for granted our long lives and freedom from plague and infection, but this is unprecedented in human history.

This freedom comes with a cost. Ridding ourselves of all of these bugs has contributed to a rise in disorders of the immune system, metabolism and even the mind (See 鈥�Are antibiotics making us sick?鈥�). Taking a dose of antibiotics is like throwing a stink bomb into a subway. The criminals clear out, but so do the citizens. The rats and cockroaches remain, unfazed by the stench.

The survivors can become resistant to our weapons. Every year, die from antibiotic-resistant infections. Proclamations of an impending superbug apocalypse are overblown 鈥� these bugs primarily attack older people and those who are already ill 鈥� but it is clear that overusing antibiotics drives up resistance, and we are running worryingly low on replacements.

If we were to treat infections without killing bacteria, they . Not only could this strategy, known as anti-virulence therapy, provide alternative drugs to fight infection, it could help to restore the potency of antibiotics for when we do need them. 鈥淚f we don鈥檛 always go to them for every infection, we can preserve their use for much longer,鈥� says , an infectious disease specialist at the University of Southern California.

So how can we do it? The idea is to stop bacteria behaving badly. Before they can cause an infection, bad bugs first need to stick in places where they aren鈥檛 wanted. If they can鈥檛 grab hold, they can鈥檛 invade.

This strategy has already shown promise for treating urinary tract infections, which are particularly common in women. Most UTIs are caused by Escherichia coli, which use their hair-like pili to bind to carbohydrates on cell surfaces. But now researchers have found that if you give people carbohydrates similar to those naturally found on cells, they act as decoys. E. coli bind to the decoys, and never get a grip on the cell surfaces. As a result, the bacteria get flushed out when people urinate.

In a small , just 15 per cent of those given the simple carbohydrate D-mannose got a UTI within six months, compared to 20 per cent of those treated with antibiotics and 61 per cent of the women given a placebo. In , women who drank a solution of D-mannose didn鈥檛 get another UTI for more than six months, on average, compared with 52 days for those given antibiotics.

Daniele Porru and colleagues at the San Matteo Foundation in Pavia, Italy, who ran the trial, also found that antibiotics became more potent for the women treated with D-mannose instead. Because antibiotic-resistant bacteria are , in the absence of antibiotics, regular bugs for resources, and come to outnumber them. That means when you do need antibiotics, they are more likely to work as most of the bacteria are the vulnerable kind. When the researchers tested samples of the bacteria, that鈥檚 just what they found. 鈥淲e noted an increased sensitivity to antibiotics, and very few side effects,鈥� says Porru.

More advanced blockers are in the works too. and at Washington University in St Louis have developed synthetic mannose derivatives that may be more effective and linger longer within the body, meaning you need less to make a difference. Studies in mice show that for at least three days, and begin to clear existing infections within 6 hours. And by blocking E. coli instead of blasting them with antibiotics, the bacteria didn鈥檛 need to evolve resistance to drugs, and beneficial bacteria living in the urinary tract were left unharmed. The potential impact is big: in the US alone, are written for UTIs each year, and up to half of the people who take them . Hultgren thinks using blockers is just the kind of approach that will 鈥渓aunch an antibiotic-sparing therapeutic revolution鈥�.

If you can鈥檛 stop bacteria from sticking, the next line of defence is a long-forgotten treatment. The idea is to neutralise the toxins that bacteria produce to break open cells and gobble up nutrients. It is a strategy first used in the 1880s by German bacteriologist (above right) and his Japanese colleague . The pair injected sublethal doses of diphtheria and tetanus toxins into animals, harvested the toxin-neutralising antibodies they produced, and then used these to treat patients. This strategy eventually halved the death rate from diphtheria and tetanus, and earned von Behring the very first Nobel prize in medicine. But when antibiotics came along, anti-toxin therapy was largely abandoned.

鈥淎 lot of treatments were forgotten because antibiotics were so successful 鈥� and the loss of these is now reflected in the lack of treatment choices,鈥� says , a microbiologist at the University of Birmingham, UK. With the rise of antibiotic resistance, anti-toxin treatments are getting a fresh look.

One area in which anti-toxins have huge potential is in treating diarrhoea. Each year from diarrhoea caused by Clostridium difficile (pictured, left) an infection often acquired after antibiotic treatment during hospital stays. The solution is usually even more antibiotics, but for a quarter of patients, . In a recent trial, when people were also given a drug that neutralises C. difficile toxins, it .

The trouble is, this kind of therapy doesn鈥檛 necessarily reduce risk of death from this infection down the line. , an emeritus professor of microbiology at the University of Wisconsin in Madison, is nevertheless confident that next generation anti-toxin drugs will cover more strains of bacteria and be more effective. 鈥淭he concept is correct,鈥� Proctor says.

There is reason to hope: a lab-grown antibody to toxins produced by the common bacterium Staphylococcus aureus 鈥� known as MRSA in its antibiotic-resistant forms 鈥� can in infected mice. It is to prevent pneumonia caused by S. aureus in people on ventilators.

Another approach is to play with the relationship between dangerous bugs and our immune systems. This is tricky though. We have evolved together with bacteria in a game of cat and mouse that is millions of years old. The bacteria hide; our immune cells evolve to seek out and destroy them; bacteria evolve new ways of hiding. S. aureus, for instance, can cloak itself in human proteins, rendering it invisible to an immune system trained to ignore the body鈥檚 own cells.

There is research into stripping away such disguises, but the more promising strategy is perhaps surprising: hide the bacteria on purpose. The most devastating consequences of infection 鈥� particularly septic shock, which 鈥� are not caused by the infection itself, but an overstimulated immune system .

See no evil

One component of the cell walls of many harmful bacteria is a molecule called endotoxin. Its presence sets off an alarm triggering our immune systems to react. But despite its menacing name, endotoxin itself does no damage to our cells. Indeed, mice without the necessary gene to detect it are (though they are more likely to get infections in the first place). In studies, multi-drug resistant Acinetobacter kills all infected mice by driving them into septic shock. But when infected mice are given the experimental drug LpxC-1, which blocks the production of endotoxin, the death rate plummets. Because bacteria signal their presence in many other ways that prompt a less severe response than endotoxin, mouse immune systems eventually fight off the infections, but without setting off the alarms that send the animals into shock. Human trials may begin in the next few years.

Another strategy for thwarting harmful bacteria rather than wiping them out is to break up their social networks. For many kinds of bacteria the decision to switch from peaceful grazers to aggressive predators is a communal one. The process is set in motion by so-called quorum sensing genes, which only kick into action when there are enough relatives around. If the signals from these genes can be scrambled, the bacteria won鈥檛 attack.

This approach is appealing because it works on a more global scale, says , a microbiologist at the University of Texas Southwestern Medical Center. In principle, a single quorum-sensing inhibitor could prevent many types of bacteria from producing a whole menu of toxins. And studies in mice show that the strategy works. The trouble is, if the ploy were too effective, it could backfire; bugs that are resistant to these quorum-sensing scramblers could be more likely to survive and cause harm. Such drugs 鈥渃ould inadvertently select new strains of superbugs鈥� that pump out high levels of toxins continually, says Proctor.

It is still years away from human trials, but there may be a less risky way to achieve the same thing. It turns out that some of the harmless bacteria that live on us also get a say in whether bad bugs go on the attack. One theory suggests that their presence deters harmful bacteria from invading because they don鈥檛 want to share their plunder with strangers. Corynebacterium, a common skin inhabitant, releases compounds that suppress S. aureus infections in mice. Not only do they throttle production of S. aureus toxins, they turn up the expression of genes associated with a non-infectious lifestyle. They don鈥檛 just disarm S. aureus, they .

The golden age of antibiotics is over. We will never again develop safe, cheap, effective new ones as fast as bugs develop resistance to them. But old habits will be hard to break. Antibiotics have saved millions of lives. Even in our current age of resistance, most first-line treatments work most of the time. That means these new strategies have to clear a very high bar before doctors take them seriously. 鈥淲e will almost have to get to the post-antibiotic era before that happens,鈥� says Proctor.

None of these strategies is a silver bullet. But they may provide alternatives, help make existing antibiotics more effective, and crucially, leave us less susceptible to disease. That is where their real value lies. 鈥淲e have to reconsider antibiotic use in a wider context,鈥� says Piddock. 鈥淲e don鈥檛 want to disrupt the microbiome and inflict collateral damage.鈥�

If we don鈥檛 reassess our use of antibiotics, we may have traded freedom from bacterial plagues for death by a host of other ailments. Obesity, fatty liver disease, diabetes, arthritis, inflammatory bowel disease, multiple sclerosis, asthma, anxiety and depression have all been linked to use and overuse of antibiotics. Without the ability to fight off infections, modern life would be impossible, but we also need to preserve the microbial communities so crucial to our health and well-being. It鈥檚 time we learned to get along.

This article appeared in print under the headline 鈥淟iving with the enemy鈥�