Melanoma cancer therapy’s efficacy may depend on the existence of specific gut bacteria

Ipilimumab is a monoclonal antibody (mAb) that binds to, and activates T-cells. (Technically, the drug binds to the CTLA-4 receptor on T-cells, which decreases T-cell suppression)  It is currently an approved therapy for the treatment of metastatic melanoma.  Unfortunately, activation of the immune system can damage the microbiome, and taking iplimumab often results in adverse side effects in the gut, such as diarrhea.  Scientists from France were studying the effect of the drug on the microbiome when they discovered that its efficacy was actually dependent on the presence of certain gut bacteria.  They published their results in the journal Science.

First, the scientists administered the ipilimumab to three groups of mice that had been given cancer through an established model.  One group of mice had a normal microbiome, the second group was germ-free, and the final group had a normal microbiome, but then were given antibiotics.  Surprisingly, the mAb activated much fewer T-cells and was much less effective in destroying the cancer in the mice that were germ free and had been given antibiotics compared to the normal mice.  In addition, the scientists noted that intestinal inflammation occurred in the normal mice, but less so in the others.  Next, the scientists measured the microbiome changes as a result of administration of the mAb, and observed a rapid decrease in Bacteroidales, Burkholderiales, and an increase in Clostridiales.  The scientists then inoculated cancerous mice with specific bacterial species prior to administration of the drug, and then measured the drug’s efficacy.  Remarkably, specific species, such as Bacteroides thetaiotaomicron were able to reestablish the drug’s therapeutic potential and decrease inflammation.

The microbiome’s complex dynamic with the immune system once again presents itself, this time by modulating the efficacy of ipilimumab.  The scientists did do some work on humans, and they noted that not all human patients suffering from melanoma and taking ipilimumab have those beneficial bacteria in their stool.  The scientists did not discuss whether their existence was associated with the cancer’s progression in humans, although it would be interesting to see.  Ipilimumab is just one of many drugs that use the immune system to attack cancer.  Continued research is needed on the microbiome’s impact on these drugs.

Diet and microbiome may influence cognitive flexibility

There has been a lot of press recently about the microbiome’s impact on mood and behavior, the so-called ‘gut-brain axis’, and it appears now more than ever that the gut microbiome has a substantial impact on the brain.  A new paper out of Oregon State University, published in the journal Neuroscience, furthers this research by showing that different diets affect mice’s cognition and memory via changes in the microbiome.

Scientists fed groups of mice a normal chow and then switched their food to either high fat, or high diets, along with continuing some on the normal diet.   The researchers then put them through a battery of cognitive tests, all the while measuring their microbiomes using stool samples.  The mice on the high sucrose and high fat diets each had similar alterations of their microbiomes, such as an increase in Clostridiales and a decrease in Bacteroidales.  Mice on the high sucrose diet had decreased scores in their cognition tests, including memory and spatial reasoning tests, which corresponded to changes in the microbiome. For example, an increase in Lactobacilli was associated with a decrease in spatial reasoning.  Mice on the high fat diet, on the other hand, showed impaired working memory, which was associated with an increase in bacteroidales.

Some of these bacteria, such as Lactobacillus are used in probiotics to increase cognitive function, and there is some scientific basis for these effects, even though this study observes a somewhat different results.  The changes in this study though, were a diet intervention, which is more complex than a simple probiotic intervention.  That being said, we must remember that microbiome science is still developing, so each of these studies should be considered in the broader context of the field before any real conclusions can be made.