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.
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.”
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).
“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.”
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.
Methods: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors or saline placebo.
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)
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)
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
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
Among 6534 of 16 622 students with a baseline BMI in the 85th percentile or higher (39.3%), BMI reporting had no effect on BMIz 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.
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.
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
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.
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.
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.
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)
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.
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…