Microbes again...and how they may be associated with improved response to anti-PD-1 for melanoma patients...and you might even laugh!!!

This past November I posted this:  Back to the cooties in our guts....again!!!

In June, 2017, there was this:  ASCO 2017: Melanoma, anti-PD1 and the microbes in your gut

In February of that year:  Antibiotic use MAY decrease effectiveness of immunotherapy?????

From 2016, there was this:  Intestinal bacteria as a way to determine risk for ipi induced colitis!

And in 2015...with a review of where all this bacterial mess started...there was this:  Cooties in our gut keep us skinny, smart and cure cancer!?????

With all that...now, there's this.....

The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Matsson, Fessler, Bao, et al. Science. 2018 Jan 5.

"Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients."

And, I present excerpts from:
CANCER THERAPY, Precision medicine using microbiota.  Intestinal microbiota influence cancer patient responses to immunotherapy.  Jobin. Science. 2018 Jan 7.

"…Conceptually, these findings suggest that bacteria-mediated interactions with the immune system are essential for optimal drug efficacy. However, there is limited information regarding the functional impact of the composition of the human microbiome and therapeutic outcomes in cancer patients. ...

...patients can be stratified into responders and nonresponders to immunotherapy on the basis of the composition of their intestinal microbiomes, suggesting that microbiota should be considered when assessing therapeutic intervention....

…Because microbiota have a pronounced modulatory effect on the immune system, they may enhance responses to immune checkpoint therapies...

...They observed that the strongest fecal microbial predictors of anti–PD-1 therapy response were bacterial diversity and abundance of Faecalibacterium and Bacteroidales...

... responding patients had an increased abundance of eight microbial species, including Bifidobacterium longum. The presence of this species in the intestines of tumor-bearing mice was previously found to improve anti–PD-L1 therapy. Interestingly, two species were also associated with nonresponsiveness (Ruminococcus obeum and Roseburia intestinalis). …

…introduction of A. muciniphila to mice receiving human nonresponder FMT reversed the low response to PD-1 blockade, improving antitumor immune cell infiltration and activity in tumors. Overall, these studies report a fascinating interaction between intestinal bacteria and antitumor efficacy of PD-1 blockade in patients, suggesting that precision medicine strategies should include the intestinal microbiota as a potential treatment modifier....

... Therefore, the presence of specific strains of bacteria may be able to modulate cancer progression and therapeutics, raising the possibility that precision medicine directed at the microbiota could inform physicians about prognosis and therapy. ..."

WOW!!!  If that's not a lot of shoo shoo, I don't know what is!!!!  So...let's break it down.  Through all the reports, the good cootie is overwhelmingly Bifidobacterium. That's the doo dad found in yogurt, chocolate, kefir, sauerkraut, spirulina, pickles, kimchi, kombucha!  Now, in addition to the bifidobacterium....the other factor that does a body good is a lot of other shit.  OR, actually...a lot of other STUFF in our boo boo.  A diverse population of cooties...living happily together...improving the lives of one another BECAUSE of their differences and what each "culture" brings to the table!!  (Damn!  Sounds like what the welcoming torch of the Statue of Liberty represented all along!!!!)  At least in little mice, the presence of Ruminococcus obeum and Roseburia intestinalis led to a decreased response to anti-PD-1.  However, by giving those nonresponders a different bacteria (A. muciniphila) the NON responsiveness, was removed.

Okay!  What does all that mean??  Not, sure.  I think a lot of this data meanders back and forth between melanoma peeps and melanoma mice (not to mention koalas in one of the prior reports!!!), so it is hard to know how much we can take as the gospel.  In the end, (HA! HA!  I CRACK myself up!  Poops!  I did it again!!!) I think we've always known that live cultures in foods like kimchi, yogurt, and kefir are good for us.  We also know that, though antibiotics save lives and misery when they are needed, they can also cause harm by killing off microbes that we would actually be better off keeping around.  So....eat the best you can.  Include fiber and culture rich foods in your diet.  Take antibiotics only when you need them.  Keep a sense of humor.  Wipe front to back.  And know that despite all the Latin names...poop...really is...poop!   - c