Using Fecal Transplants to Treat Dolphins with Gastrointestinal Disease

As with humans and other animals, dolphins host complex and taxonomically rich gut microbiomes that differ from the microbes found in their surrounding marine environment. At times, these dolphin microbiomes can experience disruptions that may lead to a spectrum of gastrointestinal ailments in these aquatic hosts. 

As part of microbiologist Jack Gilbert’s lab at the Center for Marine Biotechnology and Biomedicine at UC San Diego’s Scripps Institution of Oceanography, I recently had an opportunity to collaborate with the U.S. Navy Marine Mammal Program and the National Marine Mammal Foundation (NMMF) to study the gut microbiomes of Tursiops truncatus, commonly known as the bottlenose dolphin. The Gilbert Lab is a highly interdisciplinary group leading research in medical and environmental microbiology across multiple domains. For my PhD, I am interested in understanding how microbial communities can change following disturbances. I am exploring this topic by using time series datasets of diverse study systems ranging from environmental systems, such as rivers and coral reefs, to host-associated systems including human and dolphin gut microbiomes.

The U.S. Navy Marine Mammal Program has - since its inception in the 1960s - been dedicated to the care, training, and deployment of bottlenose dolphins and California sea lions for tasks akin to those of working K9 units. These marine mammals are trained to undertake various military functions such as ship and harbor protection, mine detection and clearance, and recovery of objects — assignments that may seem lifted off the pages of a science fiction novel. The program is based in San Diego Bay, conveniently close to Scripps Institution of Oceanography at UC San Diego. 

This project was originated by Dr. Barbara Linnehan, director of animal health and welfare at the NMMF, who began noticing that one of the dolphins in the fleet (yes, the Navy calls its groups of working dolphins a fleet) occasionally suffered from symptoms consistent with gastrointestinal disease not remedied by medication. She became interested in the possibility of taking a different approach to restoring healthy gut microbiomes in the dolphins. Fecal microbiota transplants (FMTs), or the practice of taking gut microbes from the stool of healthy donors and transplanting them to the intestinal tract of sick patients, have been practiced in human history since as early as the fourth century and is now experiencing a revival of interest in human medicine as an effective treatment for a form of colitis caused by recurrent Clostridioides difficile infection (CDI). 

Taking inspiration from established FMT protocols from human and veterinary medicine, Linnehan’s team developed a protocol to apply FMT to dolphins experiencing gastrointestinal symptoms that are non-responsive to traditional treatments such as antibiotics. They performed a series of FMT procedures on the sick dolphin and found that the dolphin made a full recovery. Additionally, the dolphin was able to be weaned off numerous medications and supportive care. 

With a single case study, however, it can be difficult to understand the underlying mechanisms behind the FMT treatment and therefore difficult to guarantee the replicability of the procedure when treating other dolphins. This warranted a larger investigation, so we conducted a clinical trial performing FMT procedures on four other recipient dolphins with either active clinical signs or a known recent history of gut dysbiosis. This time, a primary goal was to examine what was happening to the dolphin microbiome as a result of exposure to new microbes from the FMT treatment.

While directly observing the gut microbiomes inside the dolphin recipients would be challenging, stool samples fortunately provide an accurate and non-invasive proxy for what can be found within the gut environment. We collected stool samples from the recipients at pre- and post-FMT time points as well as from the healthy donors (dolphins were trained for this behavior and participated voluntarily), and performed a technique known as shotgun metagenomic sequencing that allowed us to extract pieces of genetic material from a sample. This provided an overview of the diversity and function of the microorganisms present. 

Looking through the data, I was struck by how the pre-FMT baseline communities of the dolphins mirrored the individuality of human microbiomes. It appears that there is no such thing as a “standard” dolphin microbiome. This extended to the recipient dolphins as well. There was no uniform community composition that defined the sick dolphins relative to the healthy donor dolphins.

We found that the FMT procedures were safe; we did not observe any adverse effects with any of the recipient dolphins following the procedures. We also found that this procedure tended to increase the microbial species diversity of the recipient gut microbiome. All four recipient dolphins contained new microbial species from the donor microbiome that were previously not found in the recipient’s pre-treatment microbiome. 

Importantly, the procedure once again appeared to have therapeutic benefits for the recipients. This was especially apparent with a recipient who we will call “Dolphin A,” who initially displayed particularly severe gastrointestinal issues at the start of the clinical trial. When we examined his stool sample prior to the treatment, it was apparent that Dolphin A had by far the least diverse gut microbiome out of all the dolphins in the study. Even more telling, the very few microbial species that dominated Dolphin A’s gut community were all known marine pathogens. However, post-treatment samples from Dolphin A revealed that these pathogenic microbes receded in abundance to undetectable levels, which were instead now replaced by a multitude of “good” bacterial species from the healthy donor samples. 

The FMT procedure appeared to increase the diversity of the microbial community in Dolphin A’s gut to levels similar to the healthy donor dolphins, which may have made it harder for the pathogens to remain so dominant. Within a week of the first FMT treatment, Dolphin A became healthy again, and this effect has persisted to this date, over two years since the end of the study.

Overall, we found that FMTs can be done safely in dolphins and that they can be very effective in treating animals with gastrointestinal disease and dysbiosis. Microbes can exist along a spectrum of symbiosis to their hosts, ranging from harmful pathogens to beneficial allies. And while traditional antibiotic treatments still remain useful for resolving many gut-related diseases, they are typically designed to destroy gut microbes indiscriminately, often reducing overall microbial diversity and potentially killing off beneficial bacteria that are actually preventing the growth of pathogens. As such, having therapeutic options that do not rely on antibiotics may be valuable tools for marine mammal veterinarians. 

This project was a promising first step for future studies to build upon, and we are hoping to expand further on this research area. Stay tuned for more emerging research on this topic!

Sho Kodera is a fourth-year graduate student in the Gilbert Lab working with microbial community ecology in environmental and host-associated ecosystems.