Gut Microbiome and Gestational Diabetes Mellitus
Condition: Gestational Diabetes Mellitus
MeSH terms: Diabetes, Gestational; Diabetes Mellitus
Study type: Interventional

Summary: 
      The purpose of this study is to document the gut microbiome in the 1st, 2nd and 3rd trimester
      among pregnant women with gestational diabetes and non diabetic controls.
    

Detailed description: 
      The gut microbiome:

      The human body is colonized by a multitude of microorganisms whose collective genome, the
      microbiome, complements and enhances our own genome. From this perspective, humans are
      "supra-organisms" colonized by a number of microbial cells that is 10 times greater than the
      sum of all our human somatic and germ cells, and carrying 150 times more genetic information.
      The intestine contains the largest collection of microbes among all of our body's "habitats".
      In the colon, for example, bacteria reach densities of 1011 cells per gram of luminal
      contents. Together, gut microbes form a community, or microbiota, that has a major impact on
      health through interactions with host cells (including components of the innate and adaptive
      immune systems), through extraction of nutrients and energy from the diet, and through
      complex biotransformations of a variety of ingested compounds, including potential
      carcinogens. One of the main measures tested when analyzing bacterial populations is
      diversity - identifying the different microbial components in the population, and describing
      how similar they are to one another (according to phylogeny) both within a sample and between
      samples.

      Changes in the gut microbiome: The majority of gut microbes are generally viewed as
      beneficial symbionts, but recent work has revealed that the wrong combination of beneficial
      microbes can be harmful. Shifts in the composition of the microbiome occur at different
      stages in life, such as childhood, aging, and pregnancy. Changes in the composition
      (dysbiosis) are also associated with a growing list of diseases, such as obesity,
      inflammatory bowel disease (IBD), diabetes, metabolic syndrome and others. Such associations
      raise the question of whether the dysbiosis contributes to, or is, a symptom of the disease.
      Microbiome transplant experiments have demonstrated a role of the microbiome in several
      diseases: several phenotypes could be transferred via the microbiota, such as enhanced fat
      gain, metabolic syndrome, colitis and recently, fecal transplantation from lean human
      subjects to human subjects with metabolic syndrome was shown to increase insulin sensitivity.
      Fecal transplantations have also been used successfully to treat IBD patients. Together these
      transplantation-based studies imply that the specific composition of the microbiota can be an
      important factor in the onset, and possibly the progression of chronic diseases. Thus, the
      gut microbiota may be considered, by extension, a factor in host fitness.

      Diet and the microbiome: One of the factors that most influences the composition of the
      microbiome is diet. Changes in diet influence the relative abundance and composition of the
      microbiota almost immediately, but for these compositional changes to become stable, the
      dietary change has to be long term. A few examples of recent studies on how the diet impacts
      the microbiota are mentioned below. In humans, an increase in the ratio of
      Bacteroidetes/Firmicutes is observed when restricting the calorie/carbohydrate content.
      Reduced dietary intake of carbohydrates has also been shown to result in decreased
      concentrations of butyrate producing bacteria. The type and quantity of dietary fat and
      carbohydrate have also been shown to alter the gut microbiome of people with metabolic
      syndrome. Other bacteria, Prevotella for example, are associated with high intake of
      carbohydrates and simple sugars.

      A diet high in fiber has been shown to be associated with an increase in Bifidobacterium,
      Lactobacillus, Enterococcus and Ruminococcus. Ruminococcus was also shown to increase in
      abundance in subjects on a resistant starch diet. Changes due to diet have also been
      described in mice. For example, a high fat diet can profoundly alter the composition of the
      microbiota towards an enrichment of Firmicutes.

      The female microbiome: Women go through several major physiological transitions during their
      lifetime, beginning with puberty, followed by conception, pregnancy and finally menopause.
      During these changes the female body undergoes hormonal, metabolic, immunological changes,
      and changes in the microbiome.In a pioneering study the investigators recently showed that
      gut microbiota is profoundly altered in pregnancy (and changes dramatically during gestation)
      as compared to that in non-pregnant women. Together with what the investigators know about
      changes in the female vaginal microbiome (reduced microbial richness and diversity in
      pregnancy along with an enrichment of Lactobacilli) and other microbial changes that are
      unique to women (such as dramatic shifts in hormonal levels) - ] the investigators expect
      that different pathologies will be correlated with alterations in the microbiome.

      In the proposed research, the investigators aim to test whether there is a correlation
      between gestational diabetes melitus and changes in the microbiome, as well as when the
      changes started and how glucose balance with diet changes will alter the microbiome.

      The aims of the study:

        1. To find out the differences in the microbiome composition between trimesters in healthy
           pregnant women

        2. To find out the differences in the microbiome composition between GDM and healthy
           pregnant women during all trimesters

        3. To find out the differences in the microbiome composition between balanced sugar GDM
           with diet and healthy women (without GDM) from GDM diagnosis till third trimester
    

Intervention name(s): Dietary, Exercise and lifestyle modifications
Intervention type(s): Behavioral
Intervention description(s): Women without GDM will receive advise on diet, exercise and lifestyle modifications similar to what is advised to women with GDM
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science