The Microbiome and Prader-Willi Syndrome

demons

Prader-Willi Syndrome (PWS) is a rare condition that can result from three different kinds of genetic errors — deletion, uniparental disomy, or imprinting mutation. The newborn generally starts out with feeding difficulties and seems unable to thrive. As childhood progresses, the patient develops a voracious appetite which has been attributed to an overproduction of the “hunger hormone” called ghrelin.

The constant desire to eat entails a high risk of obesity and diabetes. There are other endocrine abnormalities, like a deficiency of human growth hormone, and patients may experience dental problems, sleep disorders, scoliosis, or skin picking. The Foundation for Prader-Willi Research forthrightly states that currently there is no cure, and adds that:

To date, no medications have proven effective in regulating appetite in PWS, and therefore, strict environmental control and constant supervision are the only ways to prevent life-threatening overeating and extreme obesity at present.

Finally, management and treatment of the psychiatric and behavioral issues associated with PWS also can be very challenging. A combination of behavioral therapy, environmental control, and medication may be needed.

In the face of this discouraging prognosis, researchers are trying out or contemplating several paths — genetic manipulation, appetite-curbing drugs, cognitive therapy, electric stimulation of the brain, and more.

A small but intriguing study hints that what has up until now proven to be an intractable condition might be vulnerable to intervention. The small number of subjects is not surprising because PWS is, after all, a very rare condition. To put this information together must have taken a lot of outreach. The credits include numerous author names from 12 institutions in five countries.

The study

The August 2015 issue of EbioMedicine published the study by Prof. Liping Zhao and colleagues showing that obese children “have similar gut microbiota dysbiosis regardless of their genetic makeup, whether it is simple obesity (no underlying pathology) or genetic obesity (Prader-Willi syndrome).” The editors noted that the microbiome profile was changed by a four-week dietary intervention.

According to the report:

A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation.

To speak of a “potentially effective target for alleviation” is sober, responsible scientist talk for “This might actually work!” Time will tell whether it is a major breakthrough, or just another promising, but misleading, path.

When interviewed for the High Intensity Health podcast, Prof. Liping Zhao specified that the patients’ diet, derived from traditional Chinese foods and medicines, was “helpful, recovering their gut microbiome, losing weight and recovering from associated issues.”

The Foundation for Prader-Willi Research elaborated on what happens when the wrong kinds of organisms take over:

The altered gut bacteria balance allows more absorption of calories with increased weight gain on fixed oral calories. We hypothesize that individuals with Prader-Willi syndrome have an altered balance in gut bacteria which may influence weight gain and appetite.

Consequently, the Foundation has funded further research by Dr. Robert Schulman of Baylor College of Medicine, which is underway.

Your responses and feedback are welcome!

Source: “Diagnosis and Treatment,” FPWR.org, undated
Source: “Getting Healthier Through Microbiome Makeover,” NIH.gov, August 2015
Source: “Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children,” NIH.gov, August 2015
Source: “#123: Liping Zhao, PhD: Changing Gut Bacteria Ecology w/Chinese Medicines and Berberine,” HighIntensityHealth.com, 12/08/15
Source: “Gut microbiome in individuals with PWS,” FPWR.org, undated
Photo credit: shankar s. via VisualHunt/CC BY

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