Your microbiome and cancer

Lab studies indicate that the composition of your microbiome can help fight cancer. Your microbiome is the unique set of bacteria you carry around with you, or it might be more accurately said that they carry you around since they outnumber body cells ten to one.

Checkpoint inhibitors prevent T-cells from recognizing cancer as friend.

Your microbiome can affect immune response, which in turn can fight cancer. Unfortunately, your immune system doesn’t always recognize cancer as a threat. Solid tumors are especially hard to target. Skin and lung cancers form solid masses that are hard to penetrate compared to liquid tumors in the blood.

Cancer cells hide by fooling immune cells into thinking they are not foreign at all. To determine friend or foe, immune cells check for a protein. If they find it on cancer cells, they appear as friends.

One innovative cancer treatment involves an immunotherapy drug called checkpoint inhibitors which do just what the name suggests –they block the checkpoint that looks for friend or foe. Seeing no friend because they are blocked, immune cells mount a defense.

This is where the microbiome comes in. Gut bacteria affect our immune system’s inflammatory response. Scientists at the University of Chicago found that mice responded to cancer invasion in varying degrees according to the type of bacteria in their guts (Scientific American, April, 2016).

Mice that were fed a particular strain of bacteria were able to fight skin cancer better than those who weren’t. When poop from the cancer-fighters was transferred to others, tumor growth slowed.

Remarkably, when checkpoint inhibitors were given to both the mice with the particular bacteria and those with the fecal transplant, tumors disappeared completely in the former and was reduced in the other. Then, when the mice with the fecal transplant were also given the bacteria, they were cured completely.

French scientists had similar results in which both the checkpoint inhibitor and a different bacteria were given. Next, the scientists gave antibiotics to the mice which killed bacteria, including the beneficial ones. The conclusion is obvious: doctors need to be cautious in prescribing antibiotics to cancer patients.

Not any bacteria will do. The Chicago team used either Bifidobacterium longum or Bifidobacterium breve. The French used Bacteroides. Yogurt contains Bifidobacterium lactis or Bifidobacterium bifidum remains untested.

Fine-tuning the immune system is a tricky business. The wrong kind of bacteria could cause the immune system to become too active and attack normal tissue. Autoimmune diseases include type-1 diabetes, inflammatory bowel disease, psoriasis, and rheumatoid arthritis. The effect of general bacteria on fine-tuning the immune system still needs to be investigated.

“Obviously we need to categorize the bacteria in the human microbiome and their potential antitumor effects more completely before we can recommend any treatments in people,” cautions the Chicago team.

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Eat your vegetables, feed your microbiome

Your mother was right: vegetables are good for you. Not only do they contain essential nutrients but they also feed your microbiome with fiber.

For each of our body cells, we carry around ten microbe cells. In this light, the definition of “we” could be refined. It would be more appropriate to state that we, the microbiome, tolerate the conceit of body cells to suit our own needs. The body cells of so-called civilized societies haven’t been serving us well. Our population has declined in comparison to those in the majority world who eat more fiber and take fewer antibiotics.

It’s counterintuitive that modern societies, while relatively free of infectious diseases that cause inflammation, suffer from inflammatory diseases. Antibiotics have reduced deadly diseases while inflammatory, autoimmune, and allergic diseases are on the rise. If infection is not causing these diseases, what is?

It seems that we (microbiome et al) have traded one disease for another. In reducing infectious disease with antibiotics, we have killed off the bacteria that suppress autoimmune diseases such as asthma.

Brett Finlay, a microbiologist at the University of British Columbia, explored this connection. He found that mice treated with the antibiotic vancomycin had an increased risk of asthma later. The antibiotic had killed beneficial bacteria that are part of the clostridial group.

The clostridial group is related the scourge of hospitals: Clostridium difficile which causes death by diarrhea. But where C. difficile prompts endless inflammation and bleeding, bacteria in clostridial clusters do just the opposite—they keep the gut healthy and soothe the immune system. Moises Velasquez-Manoff explains in Scientific American:

“Scientists are now exploring whether these microbes can be used to treat a bevy of the autoimmune, allergic and inflammatory disorders that have increased in recent decades, including Crohn’s and maybe even obesity.”

The exact cause of inflammatory bowel disease remains a mystery but the picture is becoming clearer. Finlay’s findings confirm earlier results from Harry Sokol, a gastroenterologist in Paris. He ran laboratory tests on his patients with Crohn’s disease, a chronic inflammatory disorder of the gut.

All his patients had one thing in common –a scarcity of just one common bacterium, Faecalibacterium prausnitzii. Rather than “bad” microbes causing disease, maybe a could a single “good” microbe could prevent disease. Studies suggest that antibiotics may deplete the very bacteria that favorably calibrate the immune system, leaving it prone to overreaction.

Our microbiome is more integrated into ourselves than previously thought. The state of our gut influences our state of our mind. Happy bacteria love munching on plant fiber, something we get too little of. Some of the byproducts of this munching include neurotransmitters and metabolites that act on the brain.

Our brains respond through the brain-gut connection, the vagus nerve, to help calibrate our immune system. Studies on mice with sterile guts by John Cryan, a neuroscientist in Ireland, indicate how profound the effects of our microbiome is. He found that sterile mice lacked the ability to even recognize other mice with whom they interact.

We kill off gut bacteria with antibiotics, and fail to feed them with fiber at our peril; leaving us susceptible to  anxiety, depression and even autism.

Cultivate the thinner inner-you

Research indicates that you can lose weight by cultivating greater diversity of bacteria in your gut says Claudia Wells in Scientific American.

“New evidence indicates that gut bacteria alter the way we store fat, how we balance levels of glucose in the blood, and how we respond to hormones that make us feel hungry or full. The wrong mix of microbes, it seems, can help set the stage for obesity and diabetes from the moment of birth,” explains Wells.

Studies of identical human twins, one obese and the other lean, reveal that the gut bacteria of lean twins is more diverse. These Bacteroidetes specialize in breaking down bulky plant starches and fibres into shorter molecules that we can use as energy.

Studies in mice back this up. First, genetically identical mice were raised in a germ-free environment and separated into two cages. Then one group was populated with gut bacteria from an obese human twin and the other half with gut bacteria from the lean twin. Both groups were fed exactly the same. The mice with gut bacteria from the obese human twin became fatter while their siblings with lean human bacteria did not.

Then researchers, whose findings were published in the journal Science last September, moved the two groups into the same cage. The fat mice became thin because, unappealing as it may seem, mice consume each other’s feces.

Why didn’t the lean mice become fat rather than the other way around? In a word: diversity.

The researchers theorize that a diverse population of gut bacteria perform specific functions. One is to help regulate hunger so that lean people will feel full after eating. Another eliminates certain amino acids that are elevated in obese people and lead to type 2 diabetes.

While a diverse gut populations contribute to thinness, food still matters.  When mice who had become lean were fed a typical “Western diet,” they grew fat. Their siblings who were fed a diet low in fat and high in fruit, vegetables and fibre remained thin.

Growing a diverse garden of gut bacteria takes care. It starts on the day we are born when mothers give newborns a “bacterial baptism” through vaginal birth. Breast milk nurtures useful bacteria and inhibits harmful ones.

Antibiotics kill not just the weeds in this biological garden but also valuable species. “Antibiotics are like a fire in the forest,” says one researcher. They wipe out entire swathes of microbes and leave fewer to populate the gut.

Diets that are high in fat and antibiotics cause weight gain in mice and that appears to be true in humans. For ethical reasons, the design of human experiments proving the connection would be difficult.  However, circumstantial evidence exists. Maps showing obesity in the Southern U.S. line up with maps of high fat diet and high antibiotic use.

The research requires a re-thinking of who “we” are since the microbes that live in our intestines, mouth, nose, skin and genital tract outnumber “us” by a factor of ten. More realistically, what we euphemistically refer to ourselves is simply baggage that carries our vital microbial community.