Gut Bacterial Infections and Superbug C. Diff (C-difficile) eradication: Fecal Transplant Instead of Massive Doses of Antibiotics.

[Hervé]

When an FDA ruling curbed fecal transplants, I performed my own

Susan D'Agostino UnDark
Thu, 08 Nov 2018 00:01 UTC

To treat stubborn gut bacterial infections caused by Clostridium difficile, some patients have performed their own fecal microbial transplants. © BSIP/UIG via Getty Images

Doctors and policymakers have been slow to endorse the treatment - a last line of defense against the superbug C. Diff. - even as many patients have embraced it.

I'd had intestinal distress before, but never like this. I was excreting not just waste, but blood and bits of my colon's lining - up to 30 times per day. My abdominal pain hit deeper and felt less productive than the pain of giving birth, epidural-free, to my second child. Even shingles, which stung like a dental drill against my face, paled in comparison. Such was the agony of Clostridium difficile.

Commonly known as C. diff., Clostridium difficile is an antibiotic-resistant superbug carried by approximately 5 percent of the adult population. The harmful gut bacterium is normally kept in check by other, good bacteria in the gut's microbiome. But when the microbial balance is upset - for example, by a dose of antibiotics - C. diff. can gain a foothold. Left to multiply unchecked, it may kill its human host.

In 2013, the Centers for Disease Control and Prevention estimated that 14,000 Americans die each year from C. diff. Thanks to an ill-considered decision by the U.S. Food and Drug Administration, and the willful ignorance of a string of doctors charged with my care, I was nearly one of them.

Things started innocently enough. In early 2013, my doctor diagnosed me with a bacterial infection and prescribed an antibiotic. I had lived antibiotic-free for nearly four decades - a streak I was not inclined to break. But my doctor insisted on antibiotics, and I reluctantly complied.

Soon after, my stomach turned against me. I went to an emergency room and was sent home with a prescription for vancomycin, an antibiotic reserved for serious bacterial infections. But the drug proved little match for the microbes that had bum-rushed my colon. My weight and fluid loss accelerated. My colon risked perforation.

Because C. diff. spores can live for months on bedrails, doorknobs, and linens and easily shrug off common detergents and sanitizers, my master bathroom became my biohazard containment unit. There, I alternated between sitting on the toilet and lying on the floor. My husband, Esteban, brought me supplies and emotional support. My two children, 9 and 11, had been instructed to stay away. I missed them.

Desperate, I looked for C. diff. cures and treatments on my phone. That's when I learned about fecalmicrobial transplants, in which stool from a healthy donor is infused into the gut of a sick patient, to restore microbial balance.

Although the procedure has only recently gained popularity in the U.S., it's been around for ages. Academics at Nanjing Medical University in China and the University of Maryland School of Medicine noted in 2012 that fecal transplants were performed in 4th century China, during the Jin dynasty. The authors wrote that the first Chinese emergency medicine book, "Zhou Hou Bei Ji Fang" (or, "Handy Therapy for Emergencies") stated that patients dying from severe diarrhea could be cured with a swallow of a human feces suspension.

Not until 1958 did the procedure appear in modern scientific literature, in the journal Surgery. Over the decades that followed, the ancient remedy repeatedly demonstrated its mettle. In 2012, Larry Brandt of New York City's Montefiore Medical Center wrote that fecal transplantation "has been shown in numerous case series to be a rapidly acting... safe... and highly effective... therapy for recurrent Clostridium difficile infection." Nine times out of 10, he found, the stool infusions vanquished even the most stubborn C. diff. infections - sometimes in a matter of hours. One research trial comparing the efficacies of fecal transplantation and vancomycin in patients with recurring C. diff. had to be stopped for ethical reasons, when it became clear that participants assigned to the fecal transplant group were recovering while those in the vancomycin group worsened.

As I learned all this from my bathroom quarantine, I was unaware that the FDA was then moving forward with a ruling that would make it nearly impossible for people like me to access the scatological remedy: The agency had decided to classify human stool as an "investigational new drug," which would effectively bring fecal transplantation to a halt in the U.S.

The FDA's rationale was thin, at best. As Brown University and MIT researchers argued in a Nature commentary, conventional drugs "are produced under controlled conditions with consistent, known ingredients. Stool is a variable, complex mixture of microbes, metabolites and human cells. It cannot be characterized to the rigorous standards applied to conventional drugs."

Nevertheless, a handful of doctors navigated the new regulatory hurdle and continued to perform fecal transplants in clinical trials. So, when I called around about the possibility of treating my C. diff. with a fecal microbial transplant, a sensible doctor might have offered to refer me to one of those approved practitioners. Instead, everyone I talked to refused to even entertain the idea, seemingly out of disgust.

"Yuck, you don't want that. Just stay on the vancomycin," my first doctor told me. A second, a gastroenterologist, simply substituted "gross" for "yuck." A third, more tactful, expressed relief that FDA policy absolved him from having to offer the procedure.

As it turns out, such responses weren't out of the ordinary. "There is a clear discordance between physician beliefs about [fecal transplants] and patient willingness to accept [fecal transplants] as a treatment," wrote a team of U.S. and Canadian physicians, after surveying more than 100 physicians about their attitudes toward the procedure. On average, physician respondents rated all aspects of the procedure to be "at least somewhat unappealing," whereas patients had demonstrated a clear willingness to accept the C. diff. treatment.

Gastroenterologist Ciarán Kelly mused in a 2013 editorial that the unappealing aesthetics of fecal microbial transplantation might be one of the main reasons it hadn't become routine therapy for C. diff. infections. In 2012, Brandt wrote that prospective transplant recipients were being discouraged by the "intransient negativism" of physicians, who described the procedure as "quackery," "a joke," and "snake oil" - despite its track record in case series.

And so it happened that when my C. diff. roared back, worse than before, after the end of my 10-day vancomycin course, my doctor's response was to simply prescribe more vancomycin. With each subsequent treatment, however, my likelihood of recovery dropped dramatically. I started the ordeal with an approximately 70 percent chance of recovery. After months of failed antibiotic treatments, my chances had sunk below 10 percent.

My last trip to the emergency room was a grim formality. The C. diff. battle now raged beyond my colon.

"You may want to tell loved ones about your dire circumstances," my gastroenterologist said.

It dawned on me that my doctor would sooner let me die than discuss a fecal transplant. That's when I decided to do the transplant myself.

This was in the dark ages of fecal microbial transplantation, before the procedure became ingrained in the American psyche. But there were a handful of websites that offered advice on do-it-yourself fecal transplants. Some were more questionable than others. One dubiously suggested using pet feces for the donor sample.

But even with an appropriate two-legged donor, the procedure would carry risks of infections and the possibility of other adverse outcomes. My friends cautioned me against "going rogue" with an "extreme," "unapproved" treatment. But to me, the gamble was worth taking.

A New England Journal of Medicine article offered some procedural clues. For instance, my ideal donor would have a microbiome that was untainted by antibiotics. That ruled out Esteban, who had recently been administered antibiotics during an eye surgery. Ultimately, I turned to my 11-year-old daughter.

She responded openly and inquisitively, asking more questions than any of my doctors had. "Is this like in Clash of Clans when you have no troops left in your clan castle and you need someone else to donate some?" she said, referring to a popular multi-player video game.

Yes, it's exactly like that.

She agreed to do it, and at around 10 pm on a Tuesday, Esteban collected the sample. He dropped it into a blender, added saline, blended it, strained it, and poured the concoction into an enema bottle, as I lay depleted on the floor. My gut drank up the infusion as if it were dying of thirst. My colon, after five months of near-constant spasms, recovered in one transformative instant. Overnight, I went from having 30 bowel movements a day to having one. For breakfast the next morning, I ate a quesadilla loaded with black beans, cheese, salsa, lettuce, and guacamole. I've had no recurrence of C. diff. since.

Within a month of my five-month ordeal, the FDA announced a "compassionate use" exception to the restriction on fecal transplants, which gave physicians more freedom to offer the procedure to C. diff. patients. Within a year, MIT opened the first public stool bank, and the Cleveland Clinic named fecal transplantation a "Medical Innovation of 2014." Today, the stigma around fecal transplants has mostly worn off. A recent doctor, upon hearing my story, joked with a colleague that I'd had a fecal transplant "before they were cool."

I am glad that patients now have wider access to this life-saving treatment. Still, I remain wary of doctors and policymakers who once withheld that access from me and thousands of others like me. Their irrational aversion to feces - the biological agent that we all produce -nearly killed me.

Susan D'Agostino is in the MA in Science Writing program at Johns Hopkins University and is a Taylor/Blakeslee fellow of the Council for the Advancement of Science Writing.

SOTT Comment: As off-putting as the procedure may sounds, fecal transplants may just be the miracle procedure to fight off the plague of antibiotic resistant bacteria like C. diff. That doctors are so resistant to the idea likely means more and more people will be trying it themselves, or under the care of an alternative practitioner that cares more about the health of the patient than what arbitrary decision the FDA has made.

Related:

• Can a 'fecal transplant' help people lose weight?

• Research into alternatives to fecal microbiota transplant

• Good Poop! Autism symptoms show improvement from donor viruses in fecal transplants

• Fecal Transplantation: Ancient remedy used to restore gut bacteria and treat clostridium difficile infection

• Fecal transplant more effective than antibiotics for bacterial infection: study

• Fecal transplant - cure of the future?

[Flash]

I remember reading a study done in the Netherlands with stool transplant on autistic children. 30% of those receiving it recovered.

As well a stool transplant was done on obese, with stools form slim people. The obese lost weight without efforts. The reverse is also true, slim people gain weight when transplanted with stool from fat people.

[ErtheVessel]

Something else to consider in the reluctance to administer this type of incredibly potent therapy is that there is no money to be made by the pharmaceutical companies. In fact, it would potentially take money away from them because people would actually get well. Same with the diet industry angle.

[Hervé]

'Poop vault' of human feces could preserve gut's microbial biodiversity

Tania Rabesandratana sciencemag.org
Thu, 01 Nov 2018 16:31 UTC

Researchers distribute plastic bowls to collect fecal samples from Hadza people near Lake Eyasi in Tanzania. © Christopher Corzett

Whether in villages on the coast of Ghana or in the mountains of Rwanda, asking for people's poop is a good icebreaker, Mathieu Groussin says. "Everybody laughs," says Groussin, a microbiologist at the Massachusetts Institute of Technology (MIT) in Cambridge. "Especially when we stress that we need the whole fecal sample and show them the big bowl."

He's asking on behalf of the Global Microbiome Conservancy (GMC), an effort to identify and preserve gut bacteria from different peoples around the world. Most microbiome research has focused on Western, urban populations, which typically eat processed foods and use antibiotics. The few studies of traditional peoples have found a far more diverse gut microbiome that appears to be linked to the absence of certain diseases.

But as traditional societies change their lifestyles, that biodiversity is under threat, says Eric Alm, an MIT microbiologist who co-founded GMC in 2016 with Groussin and two other MIT postdocs. "Strains that coevolved with humans are currently disappearing," he says. Later this month, Groussin plans to expand the growing conservatory with samples from Nigerian communities affected by oil pollution near the Niger River delta.

Rescuing and preserving the microbes, Alm says, could pave the way for new treatments not just for gut ailments, but for other disorders linked to the microbiome-such as asthma, allergy, obesity, and diabetes.

"I'm 100% confident that there are relevant medical applications for hundreds of strains we've screened and characterized," he says.

Gathering material from human subjects and importing it to the United States for posterity raises ethical and legal complications, however. And the project itself represents a pessimistic outlook, says Stephanie Schnorr, a biological anthropologist at the University of Nevada in Las Vegas who has studied the microbiome of the Hadza, a traditional people in Tanzania.

"Keeping a biobank is already expecting that diversity loss is an inevitable process," she says.

GMC's biobank now houses about 11,000 strains, from about 40 people in seven countries. Its budget will support visits until 2021 to about 34 countries in total-from the Arctic to Africa, Asia, Oceania, and South America. After that, organizers hope to find several million dollars per year to expand the research and fund local science.

For now, the focus is on gathering strains. On collecting trips, Groussin retrieves the filled plastic bowls the morning after distributing them-or, in places with high fiber diets, within the hour. He then processes the samples in a makeshift lab in the back of a car. Portions of the stool are fixed and dried for DNA sequencing and lipid content measurement. The rest is divided into small tubes, preserved in glycerol, and shipped back to Cambridge in containers at −190°C. There, bacterial strains are isolated, using growth media that mimic the conditions of the gut, and preserved in perpetuity in large freezers.

The team is already uncovering novel strains. The 7000 strains in GMC's library that came from North American peoples include only five previously unknown genera. But the 4000 strains from Africa and the Arctic have already yielded 55 unknown genera.

Genomic data on the bacteria revealed another contrast between populations. In September, at a human microbiome symposium in Heidelberg, Germany, Groussin said GMC found preliminary evidence that so-called horizontal gene transfers between the strains living within one person are frequent enough to change the gut microbiome's function during a lifetime. These gene transfers are more frequent in industrialized populations, they found, possibly as a result of higher environmental pressures, such as antibiotic use.

Developing nations that have a history of exploitation can be wary of the effort. In Rwanda, for example, MIT researchers worked with John Rusine, director of the National Reference Library's biology lab in Kigali, to gain permission to transport stool samples to the United States. Rusine says he spent several months convincing the library's head to allow it. "Without his signature, we couldn't ship the samples out of the country." Each country keeps backup samples, and GMC trained local technicians to extract DNA. "Just keeping samples has no meaning if there is no further research here," Rusine says.

One way to ensure broad buy-in is to store samples in a territory perceived as "neutral, stable, safe, where their rights will be respected," says Maria Gloria Dominguez-Bello, a microbiologist at Rutgers University in New Brunswick, New Jersey. Dominguez-Bello leads an initiative to build an international storage facility modeled after the Svalbard Global Seed Vault, an underground cold storage building on a remote Norwegian island that safeguards plant diversity for future generations. Just as in the seed vault, researchers, institutions, or governments could make deposits in the microbiota vault, retrieve samples, and grant others access to them.

So far, the microbiota vault is just an idea, supported by a dozen volunteer scientists; it has no planned home yet, and Dominguez-Bello says she is seeking a few hundred million dollars to endow the project and get it started.

Who owns the preserved microbiome samples-and any scientific advances made using them-remains a legal puzzle. Microorganisms do fall under the Convention on Biological Diversity, a 1992 international treaty ratified by all United Nations member states except the United States. But it's not clear whether the convention applies to microbes that come from the human body.

The treaty intends to ensure that any R&D results or benefits arising from genetic resources are shared with the government or community that provided them in the first place. GMC is trying to abide by that spirit: In each country it visits, it has drawn up agreements stipulating that the stool samples and cultured bacteria strains remain the property of individual donors, and can only be used for noncommercial purposes.

But the very idea of preserving cells for future studies can be problematic, Schnorr cautions. For example, in her 2014 study of the Hadza, Schnorr used samples only in the exact way her study's consent forms described. She is skeptical that consent can be meaningful when scientists themselves don't know what questions they may ask in the future.

Kieran O'Doherty, a social scientist at the University of Guelph in Canada who has studied the ethics of microbiome research, thinks scientists should do more than archive the diversity of the human microbiome; they should look for ways to preserve it, by helping traditional peoples retain their sovereignty and natural resources. O'Doherty compares biobanking to small-scale efforts to fight climate change. "It's a good idea to use different light bulbs or drive a different car, but we need higher-level political action," he says. "To many scientists that's activism, and they're not comfortable with that."

About the author:

Tania Rabesandratana is a freelance science writer/contributing correspondent for Science.

[ramus]

I thought I would bring up..... ROUND-UP......ROUNDUP .. Contaminants In Processed Brand Name Foods

Weed killer found in more breakfast cereals, snack bars, study shows

On October 25, 2018 By Meira Gebel, Detroit Free Press

https://www.cincinnati.com/story/new...os/1757858002/

It (round up) kills the flora & fonna in the digestive tract, they spray roundup on the wheat 3 day before harvest.

Whole thread here :

https://projectavalon.net/forum4/show...74#post1234974


ROUNDUP .. Contaminants In Processed Brand Name Foods

Weed killer found in more breakfast cereals, snack bars, study shows

On October 25, 2018 By Meira Gebel, Detroit Free Press

https://www.cincinnati.com/story/new...os/1757858002/

From earlier post: ON 11th April 2017 11:34 RAMUS POSTED : Which of Your Foods are Sprayed with Round Up Just 3 Days Before Harvest? Farmers were spraying Glyphosate on their crops right before harvest to get a more uniform yield. ....... list above, link post:#4

DETROIT – A cancer-linked herbicide has been found in more than two dozen popular breakfast cereals and snack bars according to a new report released Wednesday.

Glyphosate, the main ingredient in Roundup, was found in 26 of the 28 products the Environmental Working Group (EWG) tested, in levels “higher than what EWG scientists consider protective of children’s health.”

An earlier report by EGW, an environmental advocacy organization, found similar results.

Glyphosate is the active ingredient in Monsanto's Roundup, the most heavily used herbicide in the United States. Every year, according to the EWG, more than 250 million pounds of glyphosate is sprayed on American crops.

Quaker and General Mills, though, conclude the products are safe and there is no reason for concern.


More: Weed killer in breakfast cereals: How dangerous is it?

“The tests detected glyphosate in all 28 samples of products made with conventionally grown oats. All but two of the 28 samples had levels of glyphosate above EWG’s health benchmark,” the group said in the study.