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Expanding Role of Fecal Microbiota Transplants: Hope or Hype? new
      #373933 - 12/30/19 03:03 PM
HeatherAdministrator

Reged: 12/09/02
Posts: 7795
Loc: Seattle, WA

The Expanding Role of FMT: Hope or Hype?

Restoring gut eubiosis via microbiota transplants is promising but not the all-purpose magic bullet expected by some

by Diana Swift, Contributing Writer
December 23, 2019

In January, we reported on a study by researchers from Aarhus University Hospital in Denmark showing that adding a "chaser" of fecal microbiota transplantation (FMT) was superior to antibiotic treatment with either fidaxomicin or vancomycin alone for patients with recurrent or refractory Clostridioides difficile (C. diff) infection. This follow-up describes further developments in the exciting field of FMT.

That January study reinforced already solid evidence and recent Infectious Diseases Society of America guidelines that recommend FMT as part of standard care for controlling this sometimes lethal nosocomial threat.

But along with success, some red flags began to wave. Two cases of C. diff transmission prompted a national alert from the FDA in June warning clinicians to be aware of FMT risks and to share this knowledge with prospective patients.

This alert was echoed in amplifying calls for stricter criteria and screening standards for FMT stool donors. In October, a group from Massachusetts General Hospital in Boston reported details of the two cases that prompted the FDA warning. Two immunocompromised FMT trial patients became infected with extended-spectrum beta-lactamase (ESBL)"producing Escherichia coli the day after undergoing FMT with stool from the same donor. That suggested that in addition to stricter donor standards, the risk-benefit balance of stool transplants per se need more scrutiny. "The two reported cases represent the tip of the iceberg of that FMT-transmitted infection," one observer commented.

Also in October, researchers from another Boston group at the Massachusetts Institute of Technology released a new conceptual framework for rationally selecting appropriate stool donors based on specific variations in patients' microbiomes, a move they said would increase the chance of clinical effectiveness and reduce the chance of false-negative outcomes.

November saw the publication of a Dutch study from Leiden University Medical Center reporting the first human transmission of Blastocystis subtypes 1 and 3 from donors to patients undergoing FMT for recurrent C. diff infection. Since transmission produced no gastrointestinal symptoms and did not impact treatment outcome, however, the authors surmised that the presence of this common parasite might not disqualify an FMT stool donor. The researchers, however, did observe a non-significant trend toward an increased rate of C. diff relapses and new episodes in patients treated with stool from Blastocystis-positive donors.

The general success of FMT in C. diff has sparked interest in its use for controlling other diseases such as inflammatory bowel disease (IBD). Results have been mixed, but in January of this year a small randomized trial from the University of Adelaide in Australia found that a three-dose, one-week induction course of anaerobically prepared donor FMT was more likely to induce clinical and endoscopic remission in active mild-to-moderate ulcerative colitis at week 8 than was autologous FMT. The study also showed a significant difference in favor of donor FMT for clinical remission and clinical response.

In May, results from Boston researchers in the ICON study presented at Digestive Disease Week (DDW) showed that FMT was safe and effective for IBD patients who also had C. diff infection.

Also, a small pilot study of primary sclerosing cholangitis patients by the same Boston group found FMT reduced alkaline phosphatase levels in 30% of patients and safely increased microbial diversity in all patients as early as week 1.

In liver cirrhosis patents with recurrent hepatic encephalopathy, a small randomized trial published in May by investigators from Virginia Commonwealth University in Richmond suggested FMT after antibiotic therapy might prevent long-term recurrence. The study also found long-term improvement in cognitive function.

Increasingly, FMT delivered to the gut is being tested as a gastrointestinal portal for treating metabolic and other diseases that are not specifically gastrointestinal. Also at DDW, researchers from Brigham and Women's Hospital, Boston, presented results from the first randomized controlled study of FMT in obesity showing that FMT capsules from a lean female donor changed the composition of the gut microbiota of otherwise healthy obese patients " opening the door to a possible new and much-needed stratagem for weight loss. FMT did not, however, improve levels of glucagon-like peptide-1 or alter body weight. Future studies will likely shed light on the role of the intestinal microbiome in obesity and lead to targeted therapies.

In still another DDW presentation, slightly greater numeric improvements in insulin sensitivity emerged in obese patients given FMT versus placebo, although the improvements were not statistically significant. The authors concluded that this procedure alone may not be enough to significantly help most obese patients.

Not all the studies have been positive. In July, researchers from Albert Einstein College of Medicine in New York City reported disappointing results in a randomized trial of FMT for diarrhea-predominant irritable bowel syndrome. FMT failed to improve symptom severity, quality of life and depression scores, or Bristol stool form scale values.

In contrast, at October's United European Gastroenterology Week in Barcelona, investigators in a randomized, double-blind, placebo-controlled study from Norway's University of Bergen observed that FMT using a single "super donor" with a stellar microbial signature was effective and well tolerated for various types of irritable bowel syndrome. It resulted in high rates of clinical response and marked improvement in symptoms.

Acknowledging the importance of the gut-brain axis, researchers are also investigating the FMT for other microbiome-associated conditions such as Parkinson disease. In June, a Chinese group outlined the promising case of a patient with Parkinson's and constipation whose evacuation difficulty and tremors improved after FMT.

And at the University of Ghent in Belgium, the first randomized, double-blind, placebo-controlled trial of FMT in Parkinson patients is winding down at year's end. The analysis will report soon on the effects of gut dysbiosis and restoration of gut homeostasis on the development and progression of Parkinson's disease.

Central to the success of all types of FMT trials may be the selection of ideal stool providers " the "super donors" " with favorable microbiota profiles optimally matched to the diseases and patients under study. Although it's early days and FMT is still in its infancy, such donors may prove to be elusive recruits over the long term.

https://www.medpagetoday.com/gastroenterology/generalgastroenterology/84089?xid=nl_mpt_SRGastroenterology_2019-12-29&eun=g379602d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=GastroUpdate_122919&utm_term=NL_Spec_Gastroenterology_Update_Active

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Postcolonoscopy Antibiotics Linked With IBS new
      #373950 - 06/02/20 02:14 PM
HeatherAdministrator

Reged: 12/09/02
Posts: 7795
Loc: Seattle, WA

June 01, 2020

Antibiotic exposure within 14 days after screening colonoscopy may increase risk of irritable bowel syndrome (IBS), based on a retrospective analysis of more than 400,000 individuals.

Antibiotic use in the 2 weeks leading up to colonoscopy also trended toward an association with IBS, reported lead author Ravy Vajravelu, MD, of University of Pennsylvania, Philadelphia, and colleagues.

"Laboratory studies in mice have demonstrated that colon cleansing in conjunction with systemic antibiotic use can cause persistent intestinal dysbiosis," the investigators wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19. "Because perturbation of the gut microbiome is thought to be a trigger for the development of IBS, we sought to assess whether humans who undergo bowel cleanse for colonoscopy in conjunction with antibiotic exposure develop new-onset IBS or IBS-related symptoms."

According to Dr. Vajravelu, previous human studies have shown that bowel cleansing or antibiotics can alter the baseline gut microbiome, but no previous human research explored the impact of both triggers at once.

The present study involved individuals 50 years or older from the OptumInsight Clinformatics database who underwent screening colonoscopy between 2000 and 2016. Those with preexisting gastrointestinal conditions or symptoms within 180 days leading up to colonoscopy were excluded, leaving 402,259 individuals in the final cohort. From this group, individuals were identified who had exposure to antibiotics within 14 days before and/or after colonoscopy.

The primary outcome was a diagnosis of IBS in the 180 days following the antibiotic exposure window. Secondary outcomes included newly diagnosed diarrhea, change in bowel habits, and abdominal pain. A variety of covariates were tested through multivariable logistical regression, including gastrointestinal infections, medical comorbidities, and demographic factors, with only sex and age remaining in the final model.

Across the cohort, 2% of patients received antibiotics either before or after colonoscopy, while 1% had exposure both before and after. A total of 1,002 individuals (0.2%) were diagnosed with IBS within a median time frame of 112 days.

Multivariate analysis revealed that individuals exposed to antibiotics in the 14 days following colonoscopy had a 77% increased risk of developing IBS (adjusted odds ratio, 1.77; 95% confidence interval, 1.31-2.39). To a lesser degree, and not quite achieving statistical significance, trends toward an association were found for antibiotic exposure before colonoscopy (aOR, 1.38; 95% CI, 0.99-1.92), and for antibiotic exposure both before and after colonoscopy (aOR, 1.41; 95% CI, 0.97-2.04).

Dr. Vajravelu said that these preliminary findings are currently undergoing further analysis.

"In particular, we are interested in determining whether antibiotics that target gram-negative bacteria, which are abundant in the gut, have a greater association with subsequent IBS," Dr. Vajravelu said.

In addition, they are taking steps to eliminate other confounding factors.

"The main objective of these new analyses is to ensure that the association between bowel cleanse and antibiotics with subsequent IBS is not related to the reasons antibiotics were prescribed initially," Dr. Vajravelu said. "For example, someone experiencing diarrhea could receive a trial of empiric antibiotics and then receive a colonoscopy when the diarrhea does not resolve. In [the present analysis], we avoided including individuals like this by including only those who underwent screening colonoscopy, and therefore did not have any prior documented GI symptoms. In our [ongoing] analyses, we are including additional restrictions to strengthen the findings."

If the findings do hold, Dr. Vajravelu suggested that they may have clinical implications.

"[I]t may be important to review whether patients scheduled for colonoscopy have received recent antibiotics and warn them to avoid antibiotics after colonoscopy, if possible," Dr. Vajravelu said. "Additionally, for gastroenterologists, these data may underscore the importance of adhering to preprocedural antibiotic prophylaxis guidelines put forth by GI societies."The investigators disclosed relationships with Merck, Pfizer, Gilead, and others.

Digestive Disease Week (DDW) 2020: Abstract 404.

This article originally appeared on MDEdge.com.
https://www.medscape.com/viewarticle/931491

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Heather is the Administrator of the IBS Message Boards. She is the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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Top 25 recommendations for IBS from the American College of Gastroenterology new
      #373966 - 12/15/20 03:38 PM
HeatherAdministrator

Reged: 12/09/02
Posts: 7795
Loc: Seattle, WA

December 15, 2020

ACG develops additional guidelines for treatment of IBS

The American College of Gastroenterology developed clinical guidelines for the treatment of irritable bowel syndrome.

“We believe that the information provided in this guideline will help guide both practitioners and researchers for years to come,” Brian E. Lacy, PhD, FACG, from the Mayo Clinic in Jacksonville, Florida, and colleagues said in recommendations published in the American Journal of Gastroenterology. “However, as this extensive project evolved, we recognized that there are still significant gaps in our knowledge. Future research is needed to better understand the role of the gut microbiome in patients with IBS and to understand the genesis of visceral pain.”

Lacy and colleagues used Grading of Recommendations, Assessment, Development and Evaluation methodology to evaluate 25 clinically important questions. Of these, nine questions focused on diagnostic testing and 16 questions focused on therapeutic options.

Among the 25 recommendations for IBS from the ACG are:

Serologic testing should be performed to rule out celiac disease in patients with IBS and diarrhea symptoms.

Fecal calprotectin, fecal lactoferrin and C-reactive protein should be checked in patients without alarm features and with suspected symptoms of IBS and diarrhea to rule out inflammatory bowel disease

Routine stool testing should not be performed for enteric pathogens in all IBS patients.

Routine colonoscopy should not be performed in patients with IBS symptoms aged younger than 45 years without warning signs.

A positive diagnostic strategy vs. a diagnostic strategy of exclusion should be used for patients with IBS symptoms to improve time to initiate appropriate therapy and cost-effectiveness.

Do not test for food allergies and sensitivities unless patients have reproducible symptoms concerning a food allergy.

Anorectal physiology testing should be performed in patients with IBS and symptoms that may suggest a pelvic floor disorder and refractory constipation.

Anti-spasmodics available in the United States should be used to treat global IBS.

Peppermint may be used to provide relief of global symptoms.

Mixed opioid agonists/antagonists should be used to treat global IBS-D symptoms.

A fecal transplant should not be used for the treatment of global IBS symptoms.

“Additional statements and information regarding diagnostic strategies, specific drugs, doses and duration of therapy can be found in the guideline,” the authors wrote.

https://www.healio.com/news/gastroenterology/20201215/acg-develops-guidelines-for-treatment-of-ibs

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Heather is the Administrator of the IBS Message Boards. She is the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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