Further evidence that the microbiome can improve melanoma cancer therapy

T stages of melanoma

Yesterday we discussed a paper that discussed how the microbiome impacted a melanoma cancer therapy.  In the same issue of Science another article was published where researchers from Chicago independently made a similar discovery - that the microbiome itself can impart an anti-tumor effect on melanoma.

The scientists were using a  common mouse model for melanoma between two different laboratories (Taconic Labs and Jackson Labs) when they noted that the cancer progressed much differently between the labs.  The Taconic mice had more aggressive cancer than the Jackson mice.  They hypothesized that one possible difference between the mice in the two labs were their microbiomes.  In fact, when the Taconic mice were given the Jackson mice's microbiomes, the Taconic mice's cancer grew more slowly.  The scientists then attempted to identify which bacteria were having the effect.  They compared the mice's microbiomes and discovered that Bifidobacteria were much more abundant in the Jackson mice.  Upon treating the Taconic mice with strains of Bifidobacterium longum and Bifidobacterium breve the Taconic mice's cancer grew more slowly.  Interestingly, the scientists discovered that the bacteria were likely increasing the activation of T-cells, because mice that had mutated T-cells did not have the microbiome-mediated anti-cancer effect.

This study points to an exciting role of the microbiome in mediating and activating the immune system to attack and destroy some cancers.  The researchers note that there are likely other microbiome bacteria that have this effect, but that they have only identified the Bifidobacteria.  Hopefully the scientists will be able to measure the effect in humans, and observe an association between patient outcome and the presence and absence of certain gut bacteria.

Clinical trial for probiotics in irritable bowel syndrome fails to show efficacy

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting about 10-15% of people in the United States alone, according to the International Foundation for Functional Gastrointestinal Disorders website. Fortunately, as described by the IFFGD, IBS is a functional disorder, meaning that while it does affect quality of life, it does not affect life expectancy. Probiotics have been studied as treatment for IBS because, as we’ve seen in many other examples of probiotic use, it is safe and rarely has any negative effects on the consumer. Some trials have shown that probiotics help relieve the symptoms of IBS; however the conclusions are controversial due to study structure and participant numbers. For this reason, scientists in Seoul, South Korea recently published a study in the Journal of Clinical Biochemistry and Nutrition, which studied the effects of a multi-species probiotic mixture on IBS symptoms using a double-blind study with a large number of participants.

Eighty-one patients participated in the 4-week-long double-blind study, with 42 people receiving a multi-species probiotic (containing Lactobacilli, Bifidobacteria, and Streptococci) and 38 people receiving a placebo. Baseline fecal samples were collected before probiotic/placebo consumption, revealing no significant difference between the two groups of participants. After consumption, the probiotic group showed a significant increase in concentrations of the probiotic bacterial strains in fecal samples, but not significant increase of levels of Bacteroidetes and Firmicutes.

In terms of symptom relief, while the probiotic group reported a greater percentage of relief, it was not significantly greater than the placebo group. This could be a classic case of the placebo effect, which is a phenomenon in which a sham treatment can actually improve symptoms because the person receiving the placebo believes it will help them. The results of this study are not concrete because there was no significant difference in symptom improvement; however there were significant increases in probiotic strains in fecal samples of the probiotic group. This study could be a step in the right direction toward relieving IBS symptoms.

Gut bacteria may prevent kidney injury

Scientists have found that short chain fatty acids (SCFAs), a product of gut bacteria, may protect the kidneys from acute kidney injury (AKI), a condition with high mortality rates that can also lead to other very serious kidney diseases. AKI is often caused by something called ischemia reperfusion injury, an injury resulting from a loss of oxygen to the tissue (ischemia) and a rush of blood back to the site (reperfusion). This instigates a cascade of events resulting in several immune cell populations accumulating at the site of the injury, causing inflammation and kidney damage.

Because AKI is a result of inflammation and because SCFAs are known to have anti-inflammatory effects, scientists in Brazil hypothesized that treatment with SCFAs could ameliorate kidney function. The results published in the Journal of the American Society of Nephrology were the first to show the protective role of SCFAs in kidney ischemia reperfusion injury (IRI). They found that when the three main SCFAs (acetate, propionate, and butyrate) were administered to mice undergoing this IRI injury, they protected the kidney from undergoing AKI.  As suspected, the SCFAs prevented an autoimmune response which resulted in less inflammation and apoptosis (cell death).

Acetate was the SCFA that was most protective to the kidney, so in another experiment the scientists administered acetate-producing bacteria to the mice.  Bifidobacterium adolescentis and Bifidobacterium longum were administered separately and each did produce acetate, as evidenced by increased acetate levels in the mice's feces. They found that these mice were protected from kidney IRI and therefore the bacteria were effective. They did note, though,  that it is unlikely the bacteria colonized the gut, so further investigation is needed.  

This study provides another example of probiotics preventing conditions that may have resulted in serious injury and even death. The bacteria in this study are already used in probiotics to treat other diseases, and so repurposing them for kidney disease should be possible.  The study also describes the anti-inflammatory effects of SCFAs, which we have written extensively about in this blog.