FMT Research & The Shawshank Redemption

In The Shawshank Redemption, Andy Dufresne (Tim Robbins) manages to escape prison by crawling through 500 yards of a filthy sewage pipe. It seems like a similar effort will be needed to find out how to benefit from fecal transplantation when given for problems like irritable bowel syndrome and metabolic disease/obesity. Some recent studies and associated editorials are noted below.

T Holvoet et al. Gastroenterol 2021; 160: 145-157. Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial

  • Key finding: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03).
  • Commentary: PW O’Toole, F Flanahan. Gastroenterol 2021; 160: 15-17. Full Text: Transplanting Microbes for Irritable Bowels or Irritated Microbes or Both?
    • This editorial stresses that trials of FMT in IBS have had inconsistent results and risks are unclear. “How many clinicians inform patients receiving FMT that the donor microbiota might include components that increase (or decrease) one’s risk of colorectal cancer?” Part of the problem is “due, in part, because a normal microbiome has not been defined.”

E Rinott et al. Gastroenterol 2021; 160: 158-173. Full text Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain

Key findings:

  • In this randomized controlled trial with 90 participants, autologous FMT (aFMT) significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02) and improved insulin resistance: insulin rebound (aFMT, –1.46 ± 3.6 μIU/mL vs placebo, 1.64 ± 4.7 μIU/mL; P = .04) (Graphical abstract below)
  • In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet–induced regain phase (all, P < .05).

Commentary: M Nieurdorp, K Madsen. Gastroenterol 2021; 160: 17-19. Full text The Promise of Maintaining Diet-Induced Weight Loss by Swallowing One’s Own Feces: Time to Provide a Do-It-Yourself Manual?

  • “These findings add support to the current body of evidence that the gut microbiota have a role in weight gain and metabolism. However, many questions remain. Indeed, although studies have shown varying degrees of effectiveness of FMT in the improvement of metabolic parameters in human participants, there has been no evidence yet that FMT can induce weight loss in obese patients.”
  • “The finding that maintenance of weight loss was only seen in the one dietary group consuming the Mediterranean diet plus green tea and Mankai supplement who received autologous FMT, would suggest that specific microbial profiles may be involved and that weight loss per se may not result in the required microbial profiles.”
Figure 1 from editorial: Challenges associated with the use of fecal microbial transplantation (FMT) as treatment

My take: Both of these studies show that modulation of the fecal microbiome may be helpful under the right set of circumstances to help with both irritable bowel syndrome and metabolic syndrome. However, ‘hundreds of yards’ of more research is needed to determine if this is really feasible and to assure that the benefits outweigh the potential risks.

Related blog posts:

Effects of Fecal Microbiome Transfer in Adolescents With Obesity

KSW Leong et al. JAMA Netw Open. 2020;3(12):e2030415. doi:10.1001/jamanetworkopen.2020.30415 (full text): Effects of Fecal Microbiome Transfer in Adolescents With Obesity Thanks to John Pohl’s twitter feed for this reference.

Methods: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors or saline placebo.

Key findings:

  • In this randomized, double-masked, placebo-controlled trial of 87 adolescents with obesity, FMT alone did not lead to weight loss at 6 weeks.
  • There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life
  • In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007)

Related blog posts::

Sandy Springs, GA

Best Studies from Pediatrics

Pediatrics has provided free full publication access to what they consider their best 10 articles and 5 influential COVID-19 publications: Pediatrics2020 Best Articles Link

Here are direct links to 3 of the articles:

O Nafiu et al. Race, Postoperative Complications, and Death in Apparently Healthy Children (Video Abstact available on link) Key finding:

  • Among 172 549 apparently healthy children from a retrospective database, the incidence of 30-day mortality, postoperative complications, and serious adverse events were 0.02%, 13.9%, and 5.7%, respectively. Compared with their white peers, AA children had 3.43 times the odds of dying within 30 days after surgery (odds ratio: 3.43; 95% CI: 1.73–6.79)

K Lycett et al. Body Mass Index From Early to Late Childhood and Cardiometabolic Measurements at 11 to 12 Years. The authors followed 5107 infants from birth. Key findings:

  • At age 6 to 7 years, compared with those with a healthy weight, children with overweight had higher metabolic syndrome risk scores by 0.23 SD units (95% confidence interval 0.05 to 0.41) and with obesity by 0.76 SD units (0.51–1.01), with associations almost doubling by age 10 to 11 years. Thus, overweight and obesity from early childhood onward were strongly associated with higher cardiometabolic risk at 11 to 12 years of age.
  • In addition, obesity but not overweight had slightly higher outcome carotid intima-media thickness (0.20–0.30 SD units) at all ages

A Kempe et al. Parental Hesitancy About Routine Childhood and Influenza Vaccinations: A National Survey Key finding:

  • Hesitancy prevalence was 6.1% for routine childhood and 25.8% for influenza vaccines in this online sample of 2176 parents

How Helpful Are School-Based BMI Measurements?

KA Madsen et al. JAMA Pediatr. Published online November 16, 2020. doi:10.1001/jamapediatrics.2020.4768.Full text link: Effect of School-Based Body Mass Index Reporting in California Public Schools

Methods:  Cluster randomized clinical trial. The Fit Study (2014-2017) randomized 79 California schools (n=28 641 students) to BMI screening and reporting (group 1), BMI screening only (group 2), or control (no BMI screening or reporting [group 3]) in grades 3 to 8. The setting was California elementary and middle school

Key findings:

  • Among 6534 of 16 622 students with a baseline BMI in the 85th percentile or higher (39.3%), BMI reporting had no effect on BMI z score change (−0.003; 95% CI, −0.02 to 0.01 at 1 year and 0.01; 95% CI, −0.02 to 0.03 at 2 years)
  • Weight dissatisfaction increased more among students having BMI screened at school (8694 students in groups 1 and 2) than among control participants (5674 students in group 3).

My take: Tackling obesity will require a lot more than measuring BMIs. An interesting follow-up study would be to see if schools who reported BMIs were more likely to take other measures, such as providing nutritional counseling, improving school lunch selection, and providing opportunity for more activity/exercise.

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“Leave Overweight Kids Alone”

Aubrey Gordon provides personal insight into the issue of weight stigma in her opinion piece: NY Times Leave Overweight Kids Alone

Here a few excepts:

The war on childhood obesity reached its zenith with the 2010 introduction of the national “Let’s Move!” campaign, “dedicated to solving the problem of obesity within a generation.” It was a campaign against “childhood obesity” — not specific health conditions or the behaviors that may contribute to those health conditions. It wasn’t a campaign against foods with little nutritional value, or against the unchecked poverty that called for such low-cost, shelf-stable foods. It was a campaign against a body type — specifically, children’s body types.

In 2012, Georgia began its Strong4Life campaign aimed at reducing children’s weight and lowering the state’s national ranking: second in childhood obesity. Run by the pediatric hospital Children’s Healthcare of Atlanta, it was inspired in part by a previous anti-meth campaign. Now, instead of targeting addiction in adults, the billboards targeted fatness in children…The billboards purported to warn parents of the danger of childhood fatness, but to many they appeared to be public ridicule of fat kids…

Despite ample federal and state funding, multiple national public health campaigns and a slew of television shows, the war on obesity does not appear to be lowering Americans’ B.M.I.s. According to the Centers for Disease Control and Prevention, since 1999 there has been a 39 percent increase in adult obesity and a 33.1 percent increase in obesity among children.

Weight stigma kick-starts what for many will become lifelong cycles of shame..Yet, despite its demonstrated ineffectiveness, the so-called war on childhood obesity rages on. This holiday season, for the sake of children who are told You’re not beautiful. You’re indulging too much. Your body is wrong. You must have done it, I hope some parents will declare a cease-fire.

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Isle of Palms, SC

Bariatric Surgery Reduced Obesity’s Premature Death from 8 years to 5 years in SOS Study

A recent study (LMS Carlsson et al. NEJM 2020; 383: 1535-43) was summarized in a quick take. Essentially, obese subjects who underwent bariatric surgery survived three years longer than a control group who had not undergone surgery but lived 5 years shorter than a reference group without obesity.

The authors speculate on the reasons why the bariatric subjects continued to have a lower life expectancy than controls after surgery:

  • Above-normal BMI even after surgery
  • Irreversible effects of obesity-related metabolic dysfunction
  • Surgical complications
  • Higher risk of alcohol abuse, suicide, and trauma (including fall-related); these factors were identified in the SOS study more often than in those who had not undergone bariatric surgery

Since there have been improvements in bariatric surgery since the time of this cohort underwent surgery (1987-2001), it is possible that the average gain in life expectancy would be greater.

Here are a few screenshots:

Nutritional Risks in Adolescents After Bariatric Surgery; Prevention of Childhood Obesity; Convalescent Serum for COVID-19

S Xanthakos et al. Clin Gastroenterol Hepatol 2020; 18: 1070-81. Full Text: Nutritional Risks in Adolescents After Bariatric Surgery

This was a multicenter prospective cohort study with 226 adolescents (mean age 16.5 years, mean BMI of 52.7) who had either Roux-en-Y bypass (RYGB, n=161) or vertical sleeve gastrectomy (VSG, n=67).

Key findings:

  • At 5 years, 59% of RYGB and 27% of VSG had ≥2 nutritional deficiencies
  • The most prevalent abnormality we observed was hypoferritinemia, which affected nearly twice as many RYGB recipients by Year 5 compared with VSG.
  • Vitamin B12 status likewise worsened disproportionately after RYGB, despite similar trajectories of weight loss after VSG
  • Image below shows the prevalence of abnormal values for vitamins over time

My take: This study shows that adolescents undergoing VSG had fewer nutritional deficiencies than RYGB and provides data supporting nutritional monitoring after bariatric surgery.

B Koletzko et al. JPGN 2020 70: 702-10. Full Text: Prevention of Childhood Obesity: A Position Paper of the Global Federation of International Societies of Paediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN)

Related blog posts (Bariatric Surgery):

Related blog posts (Obesity):

 

Not Curing Obesity with Fecal Microbiota Transplantation & More on Remdesivir

A recent pilot (n=22) double-blind study (JR Allegrett et al. Clin Gastroenterol Hepatol 2020; 18: 855-63) pours cold water on the idea that repopulating one’s microbiome would be helpful in treating obesity.

In this study, the authors examined obese patients without diabetes, nonalcoholic steatohepatitis, or metabolic syndrome.  In the treatment group, patients received FMT by capsules: 30 capsules at week 4 and then a maintenance dose of 12 capsules at week 8.  All FMT was derived from a single lean donor.

Key findings:

  • There were no significant changes in mean BMI at week 12 in either group.
  • Patients in the FMT group had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001).  In addition, bile acid profiles became more similar to the donor.

My take: Though this was a small study, it suggests that changing the microbiome by itself is likely insufficient to result in significant weight loss.

Related blog posts:

JH Beigel et al. NEJM DOI: 10.1056/NEJMoa2007764 (May 22, 2020): Full text: Remdesivir for the Treatment of Covid-19 — Preliminary Report

This was a a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement (n=1063).

Key findings:

  • Faster recovery for remdesivir recipients: 11 days vs 15 days
  • Lower mortality rate: 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70, 95% CI, 0.47 to 1.04) (mortality difference did not reach statistical significance)

 

 

FMT Warning & “Get Your Butt in Gear” –Less Than 10% of Kids Meeting Guidelines for Healthy Movement

To lessen obesity, three health risk behaviors have been targeted:

  • Sedentary behavior -goal is to limit to 2 hours of screen time in 24 hours
  • Physical activity -goal is 1 hour (or more) of moderate to vigorous activity
  • Sleep duration -goal is 9-12 hours (ages 6-12 years) and 8-10 hours (13-18 years)

A recent study (X Zhu et al. J Pediatr 2020; 218: 204-9) shows that <10% of U.S. kids meet these goals.  The authors examined data (2016-17) from the National Survey of Children’s Health (NSCH) dataset (n=71,811)

Key findings:

  • 80.9% did NOT meet physical activity goal
  • 76.2% did meet screen time goal
  • 581% did meet sleep goal
  • However, only 9.4% met all 3 goals
  • Not meeting these ‘movement’ guidelines was associated with obesity, particularly in females (aOR 4.97 compared to aOR 3.99 for males)

My take: We are all made to be different shapes and sizes.  Nevertheless, we should strive for healthy behaviors and healthy eating which could improve outcomes.

USDA Changing School Rules –Policy Should Get an “F”

From NPR: More Pizza And Fries? USDA Proposes To ‘Simplify’ Obama-Era School Lunch Rules

An excerpt:

The U.S. Department of Agriculture has proposed new rules for school meals aimed at giving administrators more flexibility in what they serve in school cafeterias around the country each day.

For instance, instead of being required to offer higher quantities of nutrient-dense red and orange vegetables such as carrots, peppers and buttternut squash, schools would have more discretion over the varieties of vegetables they offer each day. In addition, students will be allowed to purchase more entree items as a la carte selections…

Critics say the proposed changes from the Trump administration amount to further rollbacks of the nutrition standards put in place during the Obama administration following the passage of the Healthy, Hunger-Free Kids Act of 2010

“In practice, if finalized, this would create a huge loophole in school nutrition guidelines, paving the way for children to choose pizza, burgers, French fries, and other foods high in calories, saturated fat or sodium in place of balanced school meals every day,” The proposal follows a spate of rule changes announced by Perdue in 2018 that weakened the whole grain requirements and gave school administrators more leeway to serve up white breads and biscuits. 

My take: School lunch standards do not need to be rolled back.  While improving nutrition at schools will not solve the epidemic of obesity, it needs to be at least one piece of a much bigger puzzle.

Related blog posts: