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

Early Psychosocial Environment and Cardiometabolic Risk

“It is easier to build strong children that to repair broken men”

-Frederick Douglass

This quote comes from a previous lecture on adverse childhood experiences (ACEs) and comes to mind after reading a recent study: JR Doom et al. J Pediatr 2019; 209; 85-91.

This study examined 588 adolescents (16-18 yrs) from a longitudinal cohort that began in infancy (in Chile).

Methods: Psychosocial environmental factors including depressive symptoms, stressful life events, poor support for child development, father absence, and socioeconomic status was reported by mothers at 6-12 months of age.  These factors were analyzed to determine association with adolescent cardiometabolic parameters including BMI, higher blood pressure, anthropometric risk factors for cardiovascular disease, biomarkers for cardiovascular disease (e.g. triglycerides, HOMA, cholesterol) and metabolic syndrome

Key findings:

  • Infants with poor psychosocial environments had higher BMIs at 10 years and in adolescence, higher blood pressures, greater anthropometric risk, worsened cardiovascular biomarkers, and higher likelihood of metabolic syndrome (aOR 1.5)
  • The Figure in the article shows sequential worsening by quartiles -those with the highest risk based on psychosocial stress composite were worse on these outcomes compared to the 2nd highest risk factor quartile group. And in turn, the 2nd highest risk group >3rd highest risk group >lowest quartile.
  • “It is unknown whether these associations may be reversible.”

My take: While these results show a clear association of early life factors and worsened cardiovascular/metabolic outcomes, the mechanism for this is unclear.  Is this related to diet, less physical activity, stress hormones, a combination or other factors?

Related blog post:

NY Times: Cutting Sugar Improves Children’s Health in Just 10 Days

Perhaps this is not the best day of the year for this topic….

A recent small study of 43 children is summarized by the NY Times: Cutting Sugar Improves Children’s Health in Just 10 Days

An excerpt:

Obese children who cut back on their sugar intake see improvements in their blood pressure, cholesterol readings and other markers of health after just 10 days, a rigorous new study found.

The new research may help shed light on a question scientists have long debated: Is sugar itself harming health, or is the weight gain that comes from consuming sugary drinks and foods mainly what contributes to illness over the long term?

In the new study, which was financed by the National Institutes of Health and published Tuesday in the journal Obesity, scientists designed a clinical experiment to attempt to answer this question. They removed foods with added sugar from a group of children’s diets and replaced them with other types of carbohydrates so that the subjects’ weight and overall calorie intake remained roughly the same.

After 10 days, the children showed dramatic improvements, despite losing little or no weight. The findings add to the argument that all calories are not created equal, and they suggest that those from sugar are especially likely to contribute to Type 2 diabetes and other metabolic diseases, which are on the rise in children, said the study’s lead author, Dr. Robert Lustig, a pediatric endocrinologist at the Benioff Children’s Hospital of the University of California, San Francisco.

My take:  For a long time, I have been telling patients that if they make only one change, I would start by eliminating sugar-sweetened beverages. While this is a small study, it reinforces the view that sugar intake needs to be limited.

This post included last year’s pumpkin (Halloween 2014):  NASPGHAN Postgraduate Course 2014 -Liver Module – gutsandgrow

This year’s pumpkin:

Screen Shot 2015-10-30 at 7.22.05 PM

Heavy Heart due to Obesity

A recent study (J Pediatr 2014; 165: 1184-9) documents a “cardiometabolic phenotype” which indicates that obesity and metabolic disease exert effects at a young age.

Design: A cohort of 281 white children from Italy were carefully studied with antropometrics, lipids profiles, blood pressure, glucose, and echocardiography. Of these children, 105 were obese (mean age 11 years) and 105 were morbidly obese (mean age 12 years); 31 had normal weight and 40 were overweight.

Key findings:

  • Heart disease: 53 had eccentric left ventricular hypertrophy (LVH), 36 had concentric LV remodeling, 44 had concentric LVH, 148 had normal echocardiograms.
  • Children with concentric LVH exhibited the most severe metabolic disturbances (graphically demonstrated in Figure 1)

Bottomline: The authors conclude that “we have identified a “cardiometabolic phenotype” occurring early in life, characterized by concentric LVH, visceral obesity, high BP, high Tg/HDL-C, and high-normal FPG [fasting plasma glucose].  This result may be clinically relevant because, in adulthood, a concentric LV geometric pattern is associated with a greater risk of CV events.”



Celiac disease and less diabetes?

While there is a well-recognized association between Celiac disease and insulin-dependent diabetes mellitus (IDDM), a recent study shows a lower prevalence of non-insulin dependent diabetes mellitus (NIDDM) and metabolic syndrome in patients with celiac disease (Gastroenterol 2013; 144: 912-17).

You-Tube LinkPatients With Celiac Disease Have a Lower Prevalence  – YouTube..Dr. Toufic A. Kabbani discusses his manuscript “Patients WithCeliac Disease Have a Lower Prevalence of Non-Insulin-Dependent Diabetes Mellitus and Metabolic Syndrome.”

A retrospective review of 840 patients with biopsy-confirmed celiac disease were compared with 840 random matched controls.  Controls were matched for age, sex, and ethnicity.  Mean age was 49.4 years.

Key findings:

  • 26 (3.1%) of celiac disease cohort and 81 (9.6%) (p <0.0001) had NIDDM.
  • 3.5% of celiac disease cohort and 12.7% of controls had metabolic syndrome.
  • Though celiac disease patients had lower BMI, these findings were still present after controlling for this variable.
  • Prevalence of NIDDM was strongly associated with age in both groups.  In celiac cohort, NIDDM occurred in 0% (n=343) of those <45, 3.1% in 45-64, and 9.3% in those >65.  In contrast, the control group had NIDDM in 3.5%, 11% and 19.3% respectively.

With regard to pathophysiology, the authors did not think the protection from NIDDM was related to malabsorption.  Evidence of malabsorption was more common in patients with CD and NIDDM than in those without NIDDM.

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Microbial transfer for metabolic syndrome?

Animal models have demonstrated an association between microbiota composition and obesity.  Now, a study shows that the transfer of intestinal microbiota from lean human donors to individuals with metabolic syndrome can improve insulin sensitivity (Gastroenterology 2012; 143: 913-16).

It is known that the small intestine has sensing mechanisms to improve insulin sensitivity via neuronal circuits and changes in microbe composition may be one of the stimuli for this mechanism.  Given the association of altered microbiota with obesity, the investigators divided 18 patients with metabolic syndrome to receive either an allogenic infusion (n=9) of gut microbiota or an autologus infusion (n=9) of gut microbiota.

All subjects underwent small bowel biopsies and then subsequently had lavage through a duodenal tube.  In the allogenic group, the infusate was derived from lean male donors (BMI <23 kg/m-squared).  Insulin sensitivity was measured before and 6 weeks after infusions.


  • Fecal microbiota of obese subjects was characterized by lower microbial diversity and higher amounts of certain microbes (eg. Bacteroidetes).
  • Peripheral insulin sensitivity improved after allogenic infusion with a median of 26.2 μmol/kg/min prior to 45.3 μmol/kg/min at the six-week measurement.  It was unchanged in those with the autologous infusion as noted in Figure 1.
  • Gut microbial diversity increased significantly after allogenic infusion 178 ± 62 –>234 ± 40 species.  It was essentially unchanged in the autologous group (from 184 ± 71 to 211 ± 50).  Heat maps (Figure 2) help illustrate the microbial changes in the subjects.
  • The authors conclude that butyrate derived from many of the increased bacterial group probably has a regulatory role in improving insulin sensitivity.  Butyrate can prevent translocation of endotoxic compounds derived from gut microbiota which can promote insulin resistance.

Perhaps in a few years, besides limiting the consumption of sugary beverages in places like NYC, beverages with “lean” microbes and or “lean” probiotics may become important.

Staggering cost of obesity

For a single individual, the burden of obesity can be enormous; for a society, the projected costs for health and economics are hard to fathom (Lancet 2011; 378: 815-25).

By 2030, this report projects that there will be 65 million more obese adults in the US and 11 million more in the UK.  This is expected to cause an additional  6-8.5 million cases of diabetes, 5.7-7.3 million cases of heart disease/stroke, about 500,000 cases of cancer, and loss of 26-55 milion life years.  The medical costs are estimated to increase $48-66 billion/year in the US.

These projections are based on expected increases in the percentage of individuals who are obese.  In 2008, approximately 32% of US adult men were obese based on BMI; in 2030, the projected number is 50-51% for men.  Among US women: 35% in 2008 –> 45-52% in 2030.

To flatten the curve on spending, we will need to look at flattening other curves.

Additional references:

  • A liver disease tsunami
  • -NEJM 2011; 365: 1597. Persistence of hormonal adaptations with weight loss. Due to persistent changes in hormones like leptin & peptide YY, hard to keep wt off -result is increased appetite.
  • -NEJM 2009; 360: 859. Composition of diet does not seem to be important. Total calories important.
  • -Pediatrics 2007; 120: suppl 4: S164-S287.
  • -NEJM 2007; 357: 370. obestiy spreads in social network.  Your friends may be more influential than your genetics.
  • -Gastroenterology 2007; 132: 2085-2276. Special issue on obesity issues.
  • -NEJM 2006; 355: 1593. Case review on obesity c DDx and mgt.
  • -Pediatrics 2003; 112: 424. Position paper on prevention in childhood.
  • -Gastroenterology 2001; 120: 669-681. (review)
  • -J Pediatr 2005; 147: 429. TV viewing predicts adult BMI.
  • -Lancet 2001; 357: 505-8. One extra soda/day incr risk of obesity by 60%
  • -NEJM 1999; 341: 1097. BMI & mortality.