On an academic level, I am not a fan of bacteria. I like viruses. Thus, I usually like the idea of using viruses to kill bacteria. But I am a huge fan of fecal bacteriotherapy, aka, poop transplants.
Someone is sick, they get antibiotics. Antibiotics kill off their ‘normal’ bacteria, and allow ‘bad’ bacteria, like Clostridium difficile, to thrive. C. diff is a dangerous, increasingly drug resistant bacteria that kills, according to Wikipedia, 300 people a day.
Fecal bacteriotherapy is replacing the C. diff patients good bacteria with gut bacteria from someone else. Gut bacteria, normally collected from fecal samples.
“HAHAHAHA POOP! POOP TRANSPLANTS! What do you do? Eat someone elses poop?? EW HAHAHAHA!”
Normally I am 100% for poop jokes, but one of my grandmothers died from a C. diff infection, so when I first heard of fecal transplants, my first instinct wasnt to laugh or gag. It was “My shit could have saved my grandmother? Shit.”
And when I say ‘saved’ I mean SAVED. 90% of patients with C. diff infections who get fecal transplants resolve the infection. Antibiotics-only control arms have to be stopped in clinical trials, because the benefit of a fecal transplant is so great.
But there are quite a few problems with the practical application of fecal bacteriotherapy. They arent a food. They arent a drug. They arent a tissue. How do you standardize and regulate fecal transplants? What is the best way to deliver the ‘new poop’? As an enema? As pills? As a liquid? Do you need fresh fecal samples? In what? Water? Saline? Something else? And all the pharmacology that goes along with those questions.
And, importantly, there isnt just bacteria in poop– There is the food you ate (what if you ate peanuts and the recipient is allergic?). There are cells– your cells. What if you have a gastrointestinal cancer, and there are tumor cells shed in your feces? What if you are HIV+ and there are infected cells shed in your feces? What about drugs or medications youve taken?
Our imagination takes ‘poop transplants’ somewhere that physicians and scientists cant. Fecal transplants are not someone literally eating a bowl of poop with a spoon, or putting someone elses poop in their butts 😐 There is science behind this approach.
A new paper came out that is getting a lot of attention– Their approach to fecal transplants simplifies some things, and still works well:
1– Getting the poop. You could make a recipient very, very sick if you give them fecal matter from a ‘wrong’ patient. There are people who, Im not joking, try this at home. Do not try this at home. This is why:
Inclusion Criteria Healthy donors must be healthy, non-pregnant adults 18-50 years of age, on no medications, with a normal Body Mass Index (BMI 18.5-25). Volunteers must pass the American Association of Blood Banks (AABB) Donor questionnaire for exposure to infectious agents, have a normal physical exam (including fecal occult blood testing negative), and general laboratory screening tests within the normal range (CBC with differential, BUN/Cr, complete liver function tests, normal glucose, lipids, and C-Reactive Protein within normal range, and negative anti-nuclear antibody). Volunteers must have no significant past medical history with the exception of past resolved traumatic injury or routine surgery (e.g., wisdom teeth extraction, appendectomy, cosmetic dentistry or plastic surgery).
Exclusion Criteria (in addition to passing AABB questionnaire for blood donors) These are virtually verbatim from Hamilton et al (18) and Bakken et al (13) or more stringent • Any past or current malignancy including GI malignancy or polyposis • Personal or Family History of inflammatory bowel disease or unexplained GI illness • History of irritable bowel syndrome, excessive gas, bloating, lymphocytic colitis, idiopathic chronic constipation, chronic use of laxatives or chronic diarrhea • Any chronic medications • Use of probiotics or any OTC aids for regulating digestion • Antibiotics within the preceding 6 months • Major immunosuppressive medications, e.g., calcineurin inhibitors, exogenous glucocorticoids, biologic agents, etc. • Systemic anti-neoplastic agents • Recent ingestion of a potential allergen (e.g., nuts, shellfish, eggs, peanuts) • History of gastrointestinal surgery (e.g., gastric bypass) or endoscopy • Metabolic syndrome • Neurological, neurodevelopmental disorder e.g. Parkinson’s disease, autism, etc. • Systemic autoimmunity, e.g., multiple sclerosis, psoriasis, vasculitis, connective tissue disease, any rheumatological or inflammatory condition • Atopic diseases, e.g. asthma and eczema, food allergies, eosinophilic disorders of the gastrointestinal tract • Chronic pain syndromes, e.g., chronic fatigue syndrome, fibromyalgia
General health laboratory testing: • CBC and differential WNL ranges for gender at MGH clinical labs. Minor excursions of the % of differential for leukocyte subsets of monocytes, lymphocytes and PMNs, or red cell indices are allowed if deemed not clinically significant by the reviewing physician. No elevation of eosinophils is allowed. Total WBC as low as 4,000 is allowed given that many healthy young males often display this finding • ALT, AST, Bilirubin, alkaline phosphatase WNL ranges at MGH clinical labs. • Electrolytes and fasting glucose WNL ranges at MGH clinical laboratories(minor excursions related to intake, for example K+ slightly below normal may be allowed at the discretion of the investigator) • BUN/Cr within normal range • Serum triglycerides, HDL cholesterol within normal range for gender • Fluorescent ANA negative (18) • High sensitivity CRP WNL (<2.4 mg/dL)
Stool testing for donors (at MGH clinical laboratories unless specified below, all results must be NEGATIVE) • Clostridium difficile toxin by PCR • Routine bacterial culture for enteric bacterial pathogens (with enrichment broth) o Include Salmonella, Shigella, Yersinia, Campylobacter, E.coli 0157. • Specialized media culture for Vibrio and Listeria • Fecal Giardia antigen (DFA) • Fecal Cryptosporidium antigen (DFA) • Acid-fast stain for Cyclospora, Isospora and Cryptosporidium • Ova and parasites (microscopy) • Helicobacter pylori fecal antigen (send out to: Mayo Laboratories, Rochester MN) • Rotavirus Enzyme Immunoassay Serologic testing for donors (at MGH clinical laboratories, all must be NEGATIVE). • HIV, type 1 and 2 • HAV IgM • HBsAg, anti-HBc (both IgG and IgM), and anti-HBs. • HCV Ab • Treponemal test for syphilis (Trep-Sure); if positive; RPR is done subsequently Healthy volunteer donors will have all tests performed within one month of donation, and viral and syphilis testing (underlined and italicized above) within 2 weeks of the donation. Volunteers will be asked to refrain from eating common allergens within 5 days of the donation (tree nuts, eggs, peanuts, shellfish) but otherwise not alter their diets. Volunteers will have an interim health query for febrile, system, and GI symptoms at the time of donation and deferred for any change in health status. Donors with acute gastrointestinal symptoms, including diarrhea, vomiting, fever and abdominal pain, will be excluded from stool donation until symptoms have resolved. All tests will be performed at CLIA certified clinical laboratories, placed in medical records, and made available to volunteers for their personal physician’s records if desired.
That is how careful you have to be when dealing with fecal transplants. DO NOT TRY THIS AT HOME.
2– Making fecal bacteriotherapy. Again, patients arent eating poop with a spoon like chocolate ice cream. Scientists collected the poop, mixed it with a saline solution, filtered it, then spun it really really fast to concentrate the bacteria. They then resuspended the bacteria in a little bit of saline, plus a chemical to protect the bacteria during freezing, and put it in a capsule to protect the bacteria until they get to where they need to be in the digestive tract. Why freezing? Because it would sure be nice if you could screen a bunch of donors, make a bunch of bacteriotherapy pills, and store them in a freezer so they are on-hand for an emergency, rather than rushing the process to make them as-needed.
3– Administering the bacteriotherapy. 20 patients with recurrent C. diff infections. 15 pills of bacteriotherapy a day for two days. 14 patients resolved their current C. diff flare-up, without antibiotics. 6 patients who didnt respond got another round of treatment, and 4 of them resolved the C. diff flare-up.
18 out of 20 patients got better from this kind of fecal transplant. That is amazing!
But the best part, is that these results match those from trials that utilize fresh fecal preparations. Which means we dont have to use fresh samples for fecal transplants to work– samples can be donated and stored for later use. If you want to make this miraculous treatment feasible, practical hurdles like this need to be cleared.
But even with these great results, I like that the authors are still well aware of potential draw-backs, if their idea becomes widespread:
Some safety concerns remain. Vomiting and aspiration are potential concerns with oral delivery of FMT, although we did not observe these complications in our study. Even with careful screening, transmission of infection is possible but was also not observed in our patients. Also, the long-term effects of microbiota manipulation are still unclear, especially in light of the increasingly recognized roles of the human gut microbiome in health and disease. These potential risks should be weighed against the significant morbidity and mortality associated with recurrent CDI and the rates of diarrhea resolution reported following FMT administration.
Swallow a fecal pill. Throw up. Heave/gag while throwing up… and inhale some of those super concentrated bacteria. That would be *terrible*. And they emphasize that they could accidentally make someone sick. But, if my grandmother was given a choice between potentially getting some unknown disease maybe (?), or dying from C. diff , Im confident in which option she would have chosen.