Clinical trial NCT04555447: Gastrointestinal Tolerability to Agavins and Impact on Host-gut Microbiota-metabolism Interactions Modulation
Official title: Gastrointestinal Tolerability to Increasing Doses of Agavins and Impact on Gut Microbiota, Fecal Metabolites, and Metabolic Biomarkers in Healthy and Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Healthy
Keywords: Prebiotics
Agavins
Gastrointestinal tolerability
Obesity
Gut microbiota
SCFA
Fecal metabolites
Agave dietary fiber
Lead sponsor: Centro De Investigación Y De Estudios Avanzados Del Instituto Politécnico Nacional-Unidad Irapuato
Sponsor class: OTHER
Collaborators: name: Centro de Estudios Cardiometabólicos S.C. (CESCAM)
name: Inulina y Miel de Agave S.A. de C.V. (IMAG)
First posted: 2020-09-18
Enrollment: 52
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Healthy and obese participants randomized into agavins (prebiotic fiber) or placebo group received the corresponding dietary supplement simultaneously
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Males and females
* Age 30 - 60 years
* BMI ≥ 30 kg/m2
* Stable body weight for at least 1 month prior to the study

Exclusion Criteria:

* Type 1 and type 2 diabetes
* Hypothyroidism
* Currently following a weight loss diet or physical activity regime for the same purpose
* Weight loss \>3 kg within 3 months before enrollment
* Use of prebiotics, probiotics, or dietary fiber supplements
* Long-term (and within the preceding month) use of antioxidants, omega-3, and omega-6 fatty acids supplements
* Strenuous exercise (\>3 hours/week)
* Concomitant use of any medication influencing appetite, weight, metabolism
* Use of metformin
* Antibiotic use 1 week prior to the study
* Alcohol or substance abuse
* Diagnosis of neurological or psychiatric disorders, like anxiety, depression, Attention-Deficit/Hyperactivity Disorder (ADHD), schizophrenia
* Active smoker
* Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) enzymes concentration \>2.5 times the highest limit value
* Creatinine \>1.2 mg/dL
* Women: pregnancy or lactation
* Previous intestinal or bariatric surgery
* Heart, brain, or thyroid surgeries within the preceding 6 months
* History of liver or pancreatic disease
* History of renal failure
* Intestinal absorption disorder
* Inflammatory bowel disease
* Established cardiovascular disease
* Active or history of neoplasia within the preceding 5 years
* Chronic use of bulk laxatives and antacids

Primary outcomes:
measure: Gastrointestinal tolerability
timeFrame: 0-5 weeks
Secondary outcomes:
measure: Appetite and satiety subjective assessment
timeFrame: 0-5 weeks
measure: Gut microbiota composition
timeFrame: 5 weeks
measure: SCFA production
timeFrame: 5 weeks
measure: Fecal metabolomics
timeFrame: 5 weeks
Other outcomes:
measure: Assessment of metabolic markers
timeFrame: 0-5 weeks
measure: Body weight determination
timeFrame: 0-5 weeks
measure: Fat mass, fat-free mass, body water, and skeletal muscle mass determination
timeFrame: 0-5 weeks
Locations:
city: Irapuato
country: Mexico
facility: Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional-Unidad Irapuato (CINVESTAV-UI)
state: Guanajuato
city: Mexico City
country: Mexico
facility: Centro de Estudios Cardiometabólicos S.C. (CESCAM)
Study officials:
affiliation: Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional-UI
name: Mercedes G. López, PhD
role: STUDY_DIRECTOR
References:
citation: Huazano-Garcia A, Shin H, Lopez MG. Modulation of Gut Microbiota of Overweight Mice by Agavins and Their Association with Body Weight Loss. Nutrients. 2017 Aug 23;9(9):821. doi: 10.3390/nu9090821.
citation: Franco-Robles E, Lopez MG. Agavins Increase Neurotrophic Factors and Decrease Oxidative Stress in the Brains of High-Fat Diet-Induced Obese Mice. Molecules. 2016 Aug 2;21(8):998. doi: 10.3390/molecules21080998.
citation: Huazano-Garcia A, Lopez MG. Agavins reverse the metabolic disorders in overweight mice through the increment of short chain fatty acids and hormones. Food Funct. 2015 Dec;6(12):3720-7. doi: 10.1039/c5fo00830a. Epub 2015 Sep 3.
citation: Santiago-Garcia PA, Lopez MG. Agavins from Agave angustifolia and Agave potatorum affect food intake, body weight gain and satiety-related hormones (GLP-1 and ghrelin) in mice. Food Funct. 2014 Dec;5(12):3311-9. doi: 10.1039/c4fo00561a.
citation: Garcia-Vieyra MI, Del Real A, Lopez MG. Agave fructans: their effect on mineral absorption and bone mineral content. J Med Food. 2014 Nov;17(11):1247-55. doi: 10.1089/jmf.2013.0137. Epub 2014 Jul 28.
citation: Urias-Silvas JE, Cani PD, Delmee E, Neyrinck A, Lopez MG, Delzenne NM. Physiological effects of dietary fructans extracted from Agave tequilana Gto. and Dasylirion spp. Br J Nutr. 2008 Feb;99(2):254-61. doi: 10.1017/S0007114507795338. Epub 2007 Aug 22.