Fecal Transplantation and the Sweet Smell of Success

fecal-transplant-1Fecal Transplantation, the Sweet Smell of Success

by Jeffrey Dach MD

A recent medical meeting was devoted to the “microbiome”, the friendly bacteria in our gut.  Apparently these little microbes are doing a lot more than we thought, busy munching away and keeping us healthy.

Occasionally things go wrong.  The over-use of antibiotics will kill off friendly bacteria, allowing the pathogenic or “bad” bacteria to predominate.  This is called “dybiosis”, disruption of our normal microbial flora.   A severe form of dysbiosis is Clostrida Difficile entero-colitis,  a dreaded complication with a high mortality rate.  Cases have been increasing on the surgical wards.Upper Left Image: Air Contrast Barium Xray of Colon courtesy of How Fecal Transplants Work

Clostridia Cases IncreasingToxins Produced by Clostridia

There are hundred of strains of Clostridia, and some produce toxins such as botulism and tetanus.  Others produce toxic metabolites which disrupt neurotransmitter function in the brain.  Hence the interest in probiotic therapy and fecal transplantation for neuropsychiatric disease such as autism, schizophrenia, parkinson’s, multiple sclerosis etc.   Upper left image chart showing increasing clostrida cases on the surgical ward .

When Probiotics Are Not Enough

Clostriia Difficile Fecal TransplantRestoring our normal gut flora with probiotics usually gets things back to normal.   If the probiotic capsules from the health food store are not strong enough, the next big gun is fecal transplantation.  This more drastic measure “transplants” the microbial flora from a normal person into the colon of the recipient.  The procedure is done with a large syringe filled with colon contents (fecal material) which is injected into the colon of the recipient.  As disgusting as this might sound, it works remarkably well for  Clostridia Difficile entero-colitis, used when antibiotics such as Flagyl and Vancomycin are no longer effective.  More than 100 US hospitals offer fecal transplantation for Clostridia difficile.  Here is a list of providers and clinical trialsAbove left image Electron Microscope view of Clostridia Difficile

Fecal Transplantation for Inflammatory Bowel Disease

crohns-disease-s7-photo-of-barium-enema-exam-with-aphthous-ulcersCrohn’s Disease:

Dr David Suskind at Seattle Children’s Hospital  reported success using fecal transplant in ten children with Crohn’s Disease in the first FDA-approved study of its type.   Seven of ten actually went into “remission” after the procedure. Left image: Typical apthous ulcers of crohn’s colitis on air contrast barium Xray of colon.  Crohn’s usually involves the terminal ileum, yet can also involve the colon as well.

ulcerative_colitis_1Ulcerative Colitis:

Thomas Borody MD reported in 2003 his experience with fecal transplant for Ulcerative Colitis. He concluded the procedure is capable of reversing the ulcerative colitis in “selected patients” (7)

Left image: air contrast barium enema of colon typical findings of ulcerative colitis with granular mucosal pattern.

Fecal Transplant for Autism, Parkinson’s and other Neurological Disease

Lately, fecal transplantation has been proposed as a treatment for many other  diseases.  For example, there have been case reports with favorable outcomes in Autism,  “Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura” (1)

David Perlmutter MD and Brain Maker

The well known neurologist, Dr David Perlmutter was one of the keynote speakers at the meeting.  His excellent presentation included video clips of  two cases of remarkable recoveries in neurological disease after fecal transplantation.  The first case was Jason, a 10 year old autistic youngster with documented dysbiosis from frequent bouts of antibiotics.  Jason and his mom, Melinda, traveled to Europe for a series of fecal transplants with remarkable recovery.

Multiple Sclerosis Case Report

The second case was a Multiple Sclerosis patient unable to walk because of his neurological disorder  After a series of  fecal transplants in Europe, his video clip showed him walking nonchalantly down the hall of his hotel.(2)  This certainly got my attention.

parkinsons4Parkinson’s Disease

A number of speakers lightly touched on studies showing utility of fecal transplant in Parkinson’s disease. (2)(11-15)

Indeed, a new study in mice published in Cell 2016 by Timothy Sampson confirms the connection between colonic microbiota and Parkinson’s disease. (11)  Their study demonstrated that human gut microbiota taken from Parkinson’s Disease patients induce enhanced motor dysfunction when transplanted into mice.  Dr Qin in 2007 showed that low level endotoxemia (LPS) from “leaky gut” causes microglial activation in the brain, and loss of dopaminergic neurons in the substantia nigra identical to the pathology in Parkinson Disease patients.(15)  Indeed, LPS induced microglial activation has become the standard animal model to study Parkinson’s Disease.(15-19)

Conclusion:

One should be cautious and not too hasty in placing too many expectations on a new therapy.  Perhaps the field of “targeted” probiotics and fecal transplantation will prove to be the next great discovery of modern medicine, providing a “cure” for Parkinson’s and other neurodegeneratice diseases.  On the other hand, only time will tell if the new modality will live up to expectations.  If not, we will certainly be disappointed.

Buy Lactobacillus Rhamnosus GG Probiotics by Culturelle on AMazon

update 2015: The Medicine of the Microbiome by Mark Davis, ND

Jeffrey Dach MD
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Articles with Related Interest:

Preventing C Diff with Probiotics

Curing Autism with Antibiotics Probiotics

Links and References

1) Xu, Meng-Que et al. “Fecal Microbiota Transplantation Broadening Its Application beyond Intestinal Disorders.” World Journal of Gastroenterology : WJG 21.1 (2015): 102–111. PMC. Web. 22 May 2015.

Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.

2) Ananthaswamy, Anil. “Faecal transplant eases symptoms of Parkinson’s disease.” New Scientist 209.2796 (2011): 8-9.

3)  Fecal Flora Transplantation February 20, 2011 Jacob Schor ND, FABNO

4) Vindigni, Stephen M., Elizabeth K. Broussard, and Christina M. Surawicz. ”

intestinal microbiome fecal transplant probiotics Clostridium difficile Vindigni 2013

Alteration of the intestinal microbiome: fecal microbiota transplant and probiotics for Clostridium difficile and beyond.” (2013): 615-628.

5) Borody, Thomas J., Sudarshan Paramsothy, and Gaurav Agrawal. “Fecal microbiota transplantation: indications, methods, evidence, and future directions.” Current gastroenterology reports 15.8 (2013): 1-7. Fecal transplantation Borody Current gastroenterology reports 2013

6) Borody, Thomas J., Lawrence J. Brandt, and Sudarshan Paramsothy. “Therapeutic faecal microbiota transplantation: current status and future developments.” Current opinion in gastroenterology 30.1 (2014): 97.

7) Borody, Thomas J., et al. “Treatment of ulcerative colitis using fecal bacteriotherapy.” Journal of clinical gastroenterology 37.1 (2003): 42-47.Treatment ulcerative colitis fecal bacteriotherapy Borodny Journal of clinical gastroenterology 2003

8) Does it All Begin W/ Vitamin K in the Gut? Vitamin K ⇆ Gut Interactions Link in Intestinal Dysbiosis, Prostate Health and an Emerging Cause of Severe Pregnancy Complications?  from muscle jenny titanium pro x.

9) Autism Case David Permutter

10) Laszlo, M., and O. Pascu. “Full Clinical and Endoscopic Remission Following Fecal Microbiota Transplant with Moderate-Severe Treatment-Resistant Ulcerative Colitis.” J Gastroint Dig Syst 4.183 (2014): 2.  Remission Fecal Microbiota Transplant Ulcerative Colitis Laszlo 2014

11)   Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease  Sampson, Timothy R. et al. Cell , Volume 167 , Issue 6 , 1469 – 1480.e12

12)  Forsyth, Christopher B., et al. “Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease.” PloS one 6.12 (2011): e28032.
Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha–synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress.

13) Kelly, Leo P., et al. “Progression of intestinal permeability changes and alpha‐synuclein expression in a mouse model of Parkinson’s disease.” Movement Disorders 29.8 (2014): 999-1009.

14)  Mulak, Agata, and Bruno Bonaz. “Brain-gut-microbiota axis in Parkinson’s disease.” World journal of gastroenterology: WJG 21.37 (2015): 10609.

15) Qin, Liya et al. “Systemic LPS Causes Chronic Neuro inflammation and Progressive Neurodegeneration.” Glia 55.5 (2007): 453–462.   Together, these data demonstrate that through TNFα, peripheral inflammation in adult animals can: (1) activate brain microglia to produce chronically elevated pro-inflammatory factors; (2) induce delayed and progressive loss of DA neurons in the SN. These findings provide valuable insight into the potential pathogenesis and self-propelling nature of Parkinson’s disease.

16) Dutta, Garima, Ping Zhang, and Bin Liu. “The lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery.” Fundamental & clinical pharmacology 22.5 (2008): 453-464.

17)  Tufekci, Kemal Ugur, Sermin Genc, and Kursad Genc. “The endotoxin-induced neuroinflammation model of Parkinson’s disease.” Parkinson’s Disease 2011 (2011).

18) Sandiego, Christine M., et al. “Imaging robust microglial activation after lipopolysaccharide administration in humans with PET.” Proceedings of the National Academy of Sciences 112.40 (2015): 12468-12473.

19)  Pal, Gian D., et al. “Abnormal lipopolysaccharide binding protein as marker of gastrointestinal inflammation in Parkinson disease.” Frontiers in neuroscience 9 (2015).
Conclusions: Our data suggests that LBP is one GI biomarker related to LPS induced neurotoxicity. However, there was significant variability in LBP levels within the PD and control groups, limiting its utility as a stand-alone biomarker. This study supports the role of LPS induced neurotoxicity in PD and further exploration of this pathway may be useful in developing sensitive and specific biomarkers for PD.

20)  Sharon, Gil, et al. “The Central Nervous System and the Gut Microbiome.” Cell 167.4 (2016): 915-932.

21) Lull, Melinda E., and Michelle L. Block. “Microglial activation and chronic neurodegeneration.” Neurotherapeutics 7.4 (2010): 354-365.

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Summary
Fecal Transplantation and the Sweet Smell of Success
Article Name
Fecal Transplantation and the Sweet Smell of Success
Description
Fecal transplant is emerging as a new medical intervention, and is FDA approved for C. Diff Entercolitis.
Author