Gastrointestinal Tolerability to Agavins and Impact on Host-gut Microbiota-metabolism Interactions Modulation
Condition: Obesity; Healthy
MeSH terms: Obesity
Study type: Interventional

Summary: 
      Agavins are branched neo-fructans and prebiotic fiber found in Agave plants. In preclinical
      studies, agavins have demonstrated an effect in reversing metabolic disorders associated to
      overweight and obesity through the modulation of gut microbiota activity and composition,
      showing their interesting potential in the context of high obesity and cardiovascular
      diseases prevalence in Mexican population. However, current information about
      gastrointestinal adaptation and effects of agavins intake in humans is scarce. We
      hypothesized that increasing amounts of agavins up to 12 g/day, will be well tolerated by
      healthy and obese adult participants, but with differences between these groups, modulating
      gut microbiota activity and structure differentially, as well as the metabolic status after a
      5-week dose-escalation intervention.
    

Detailed description: 
      Diet has dramatically changed over the past decades with increased consumption of high-fat,
      high-sugar, high-sodium processed and refined foods, but with low or very low fiber-rich
      products. Microbiota-accessible carbohydrates (MACs) found for example in dietary fiber have
      been recognized as crucial for the microbial ecosystem in the gut; the lack of these
      available carbohydrates depletes the microbial community, causing alterations in its
      composition and performance. Perturbations in the gut microbiota have been related with
      several diseases, so as reduction in dietary fiber has been linked with an increased risk for
      developing chronic diseases, namely cardiovascular and metabolic ones, such as obesity and
      type 2 diabetes. Mexico is the second country with the highest obesity rates worldwide, which
      represents a major national public health challenge. Interestingly, national nutrition
      surveys have found that Mexican adults consume less than half the dietary intake
      recommendation for fiber, along with an alarming statistic of 7 in 10 adults being overweight
      or obese.

      A change in dietary patterns intended to achieve adequate nutrient intake, dietary fiber
      included, is one strategy that could help modify this nutrition trend in the country, but
      another accessible alternative is the supplementation of prebiotic fiber, thus increasing
      fiber consumption and avoiding gut microbiota alterations simultaneously. Prebiotics, such as
      fructans, are substrates selectively used by gut microbes, modifying their activity and/or
      community composition, and conferring health benefits to the host. Clinical research has
      demonstrated their impact in reducing body weight, fat mass, hyperlipidemia, etc. Agave
      prebiotics, also known as agavins, are fructan-type carbohydrates that possess a unique
      molecular structure and are extracted as a complex multi-disperse mixture presenting
      different degrees of polymerization and/or branching. Previously, agavins have shown to
      induce weight loss, a significant reduction in glucose and total cholesterol levels, and
      promotion of satiety-related hormones in overweight mice through the increment in short-chain
      fatty acids (SCFA) and specific modulation of gut microbiota; more recently, fecal
      metabolomics have revealed interesting microbial-derived metabolites, detected after agavins
      supplementation in mouse models that could induce a beneficial effect on host health, but
      more research is needed.

      Experts have stated that differences in dietary fiber structure guide its degradation: which
      microbes can metabolize these substrates, and the effects in the microbial community that
      overall, impact health. Additionally, structural differences in prebiotic fibers like
      agavins, may cause specific gastrointestinal (GI) adaptation and tolerance which is of great
      importance to promote their consumption and in determining an ideal amount or dose to further
      explore their impact.

      In this study we propose a double-blind, placebo controlled, parallel groups, dose-escalation
      trial, where lean and obese subjects were assigned to either agavins or placebo group for a
      5-week dose-escalation period. We aim to evaluate the evolution of GI tolerability and
      compared the records between lean and obese participants (Mexican adults), the impact in gut
      microbiota composition and activity through the determination of short-chain fatty acids and
      fecal metabolites, and metabolic status, all of this after a short period of time proposed to
      induce adaptation to agavins intake.
    

Intervention name(s): Agavins (prebiotic fiber); Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Agavins contained in ready-to-use sachets were dissolved in water, and participants consumed the corresponding dose daily (2.5, 5.0, 7.0, 10 or 12 g) for 1 week, preferentially in the evening. Participants followed a 5-week dose-escalation intervention.; Maltodextrin contained in ready-to-use sachets was dissolved in water, and participants consumed the corresponding dose daily (2.5, 5.0, 7.0, 10 or 12 g) for 1 week, preferentially in the evening. Participants followed a 5-week dose-escalation intervention.
Other intervention name(s): Agave inulin (Preventy); Maltodextrin (Globe 10 IP)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Healthy and obese participants randomized into agavins (prebiotic fiber) or placebo group received the corresponding dietary supplement simultaneously
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Prebiotics; Agavins; Gastrointestinal tolerability; Obesity; Gut microbiota; SCFA; Fecal metabolites; Agave dietary fiber