3 Game-Changing Fecal Transplant Studies in 2016

Can fecal transplants not only stop superbug infections but prevent their spread?

We see a lot of the headlines in the news and it is sometimes hard to catch and process all the new information. So here’s a summary of three important new insights uncovered by researchers about fecal transplants in 2016.

FMT Strengthens Bile Acids to Prevent C. diff Spore Germination

STUDY:
Changes in Colonic Bile Acid Composition Following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination
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This was an important study in the effort to help us understand the mechanisms of why FMT is so successful for C. diff. We’ve had several theories about diversity of the microbiome and how that works to prevent the growth of C. diff.  What was very interesting about this study was that didn’t focus on the microbiome, but on how FMT changed the composition of bile acids. This change in bile acids made a significant difference in spore germination.

“Bile acids at concentrations found in patients’ feces prior to FMT induced germination of C. difficile, although with variable potency across different strains. However, bile acids at concentrations found in patients after FMT did not induce germination and inhibited vegetative growth of all C. difficile strains…These results support the idea that intracolonic bile acids play a key mechanistic role in the success of FMT…”

So basically, before fecal transplant, a patient with C. diff didn’t have the right bile salt composition to prevent the spores from growing into active C. diff bacteria.  In fact, it appears that the bile had primary salts that actually acted to spur the growth of spores into C. diff bacteria.  What I found very interesting, was that, according to the authors, the reason that the patient’s bile salts were altered was due to antibiotics.

“Because of the cytotoxic effects of antibiotics on microbiota, including normal gut microflora, it is not surprising that a variety of antibiotics, including ciprofloxacin, neomycin, and β-lactams, significantly alter the fecal bile acid pool in rodents and in vitro human fecal cultures, reducing the proportion of secondary relative to primary bile acids (5, 12, 18, 45). These findings suggest that antibiotic treatment is likely to substantially alter intestinal bacteria-mediated fecal bile acid metabolism in R-CDI patients.”

This is likely one of the reasons why antibiotics often lead to C.diff infections.  It isn’t just the dysbiosis of the microbiome.  It also has to do with how the dysbiosis affects the metabolism of bile salts and turns them into the perfect fertilizer for C.diff spores to germinate.

After fecal transplant, the bile was altered back to a normal composition to have more secondary salts, which were able to prevent the spores from germinating into C. diff.

There have actually been a couple of other studies that also reported changes in bile salts after fecal transplant, but this study was the first to confirm that the changes inhibited C. diff spore germination.

FMT May Lower Calcium Oxalate Levels to Decrease Kidney Stone Formation

STUDY:
Microbial Community Transplant Results in Increased and Long-Term Oxalate Degradation

What if a fecal transplant could replenish oxalate degrading bacteria in the colon?  Since oxalate degrading bacteria have been shown to lower the calcium oxalate levels in the blood by 70-90%, it may lead to lower kidney stones in susceptible populations.  The problem has been getting oxalate degraders to “stick” in the guts of people predisposed to kidney stones.

In previous studies, probiotics blends of the oxalate degrader bacteria, Oxalobacter formigenes, were mixed with Lactobacillus and Bifidobacteria and introduced to patients.  The recipients did see a degradation of oxalates by the bacteria and lowering of calcium oxalate in urine tests.

Unfortunately, the effects only lasted for between five days to five weeks. However, in this study, when Oxalobacter formingenes and another oxalate degrading bacteria called Neotoma albigula were introduced during a fecal transplant, the bacteria were able to persist over time.

“Microbial transplants involving the N. albigula microbiota resulted in the persistent colonization of bacteria, including O. formigenes, to the SDR and the concomitant retention of oxalate-degrading function 9 months after the transplant, indicating the robustness of the community to captive conditions. In contrast, humans and SDRs inoculated with O. formigenes alone typically exhibit a loss of the bacteria and their associated function within 5 days to 5 weeks [3436]. Some individuals can retain O. formigenes 9 months after inoculation, indicative of potentially important differences among individuals that may facilitate colonization [32]. The use of fecal microbial transplants often results in a more persistent shift of the recipient’s microbiota for several months to up to a year or more after the initial transplant [5053]”

Because this was an animal study, will need to see a human trial to be sure that it would work as well in humans.  However, since there really hasn’t been an adequate treatment for kidney stones, this discovery is exciting in its potential.

Fecal Transplants Shown to Decolonize Antibiotic Resistant Bacteria

STUDY:
Fecal microbial transplants reduce antibiotic-resistant genes in patients with recurrent Clostridium difficile infection

We are all concerned about antibiotic resistance.  However, patients who have recurrent C.diff have an extra concern because they tend to carry the strains of C.diff that are antibiotic resistant.  In addition, they also tend to have higher levels of other antibiotic resistant bacteria such as Klebsiella and Escherichia, and an increased number of antibiotic resistant genes within there microbiome.

Fecal transplant not only eliminated the known bacteria, it lowered the number of antibiotic resistant genes and kept on lowering it over time.  This means that commensal bacteria that were showing antibiotic resistance were then repopulated with nonresistant bacteria.

“Prior to FMT, the patients who responded to a single FMT had a mean of 34.5 ± 6.7 different ABR (antibiotic resistant) genes. At the first follow-up period (1-3 wks post FMT), the number of ABR genes in the RCDI patients who had a clinical response had significantly decreased to a mean of 12.2 ± 7.0. In subsequent follow-ups, the average number of ABR genes continued to drop to a mean of 5.1 ± 0.74 genes”

Each year, we discover more about how fecal transplants can positively affect human health.  POP will be there to help you make sense of the science as it becomes available.  In addition to fecal transplant studies, we’ll also be tracking the science of the microbiome.  In our next post we’ll look at what 2016 taught us about the microbiome.

 

Citations:
Millan, B., Park, H., Hotte, N., Mathieu, O., Burguiere, P., Tompkins, T. A., … Madsen, K. L. (2016). Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 62(12), 1479–1486. http://doi.org/10.1093/cid/ciw185
Miller, A. W., Oakeson, K. F., Dale, C., & Dearing, M. D. (2016). Microbial Community Transplant Results in Increased and Long-Term Oxalate Degradation. Microbial Ecology, 72(2), 470–478. http://doi.org/10.1007/s00248-016-0800-2
Weingarden, A. R., Dosa, P. I., DeWinter, E., Steer, C. J., Shaughnessy, M. K., Johnson, J. R., … Sadowsky, M. J. (2016). Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth. PLoS ONE, 11(1), e0147210. http://doi.org/10.1371/journal.pone.0147210

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