Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans
Condition: Overweight; Microtia; Endotoxemia; Metabolic Syndrome; Insulin Resistance; Non-Alcoholic Fatty Liver Disease
MeSH terms: Endotoxemia; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Congenital Microtia; Overweight; Metabolic Syndrome; Insulin Resistance
Study type: Interventional

Summary: 
      Previous work of the investigators demonstrated the anti-obesity and anti-steatosis potential
      of the Amazonian fruit camu-camu (CC) in a mouse model of diet-induced obesity [1]. It was
      demonstrated that the prebiotic role of CC was directly linked to higher energy expenditure
      stimulated by the fruit since fecal transplantation from CC-treated mice to germ-free mice
      was sufficient to reproduce the effects.

      The full protection against hepatic steatosis observed in CC-treated mice is of particular
      importance since nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of
      chronic liver disease. Thirty percent of adults in developed countries have excess fat
      accumulation in the liver, and this figure can be as high as 80% in obese subjects. NAFLD is
      an umbrella term encompassing simple steatosis, as well as non-alcoholic steatohepatitis
      which can lead to cirrhosis and hepatocellular carcinoma in up to 20% of cases. Up to now,
      except for lifestyle changes, no effective drug treatment are available. Previous work has
      suggested that CC possesses anti-inflammatory properties and could acutely reduce blood
      pressure and glycemia after a single intake. While CC could represent a promising treatment
      for obesity and fatty liver, no studies have thoroughly tested this potential in humans.
      Therefore, a robust clinical proof of concept study is needed to provide convincing evidence
      for a microbiome-based therapeutic strategy to counteract obesity and its associated
      metabolic disorders.

      The mechanism of action of CC could involve bile acid (BA) metabolism. BA are produced in the
      liver and metabolized in the intestine by the gut microbiota. Conversely, they can modulate
      gut microbial composition. BA and particularly, primary BA, are powerful regulators of
      metabolism. Indeed, mice treated orally with the primary BA α, β muricholic (αMCA, βMCA) and
      cholic acids (CA) were protected from diet-induced obesity and hepatic lipid accumulation.
      Interestingly, the investigators reported that administration of CC to mice increased the
      levels of αMCA, βMCA and CA. Primary BA are predominantly secreted conjugated to amino acids
      and that deconjugation rely on the microbial enzymatic machinery of gut commensals. The
      increased presence of the deconjugated primary BA in CC-treated mice indicate that a cluster
      of microbes selected by CC influence the BA pool composition. These data therefore point to
      an Interplay between BA and gut microbiota mediating the health effects of CC.

      Polyphenols and in particular procyanidins and ellagitannins in CC can also be responsible
      for the modulation of BA that can impact on the gut microbiota. Indeed, it has been reported
      that ellagitannins containing food like walnuts modulate secondary BA in humans whereas
      procyanidins can interact with farnesoid X receptors and alter BA recirculation to reduce
      hypertriglyceridemia. These effects are likely mediated by the remodeling of the microbiota
      by the polyphenols.

      In accordance with the hypothesis that the ultimate effect of CC is directly linked to a
      modification of the microbiota, fecal transplantation from CC-treated mice to germ-free mice
      was sufficient to recapitulate the lower weight gain and the higher energy expenditure seen
      in donor mice.
    


Intervention name(s): Camu camu; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 3 capsules of camu camu powder (500 mg / capsule) daily during 12 weeks; 3 capsules of placebo daily during 12 weeks
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention