Investigation of the Ability of a Supplement to Increase Good Bacteria in the Human Intestine and Blood Sugar Levels
Condition: Pre-diabetic
MeSH terms: Prediabetic State
Study type: Interventional

Summary: 
      This study aims to determine whether the use of a supplement called xylooligosaccharide (XOS)
      increases the number of good bacteria that live in human intestines and can maintain healthy
      blood sugar levels, and whether XOS has any unpleasant or unexpected side effects when
      consumed at different dosages. Subjects who participate in this study will be randomized to
      receive an eight week supply of either a lower dose of XOS or placebo (no active substance).
      This will be determined randomly, in a process similar to flipping a coin. Blood samples will
      be taken at each visits, including an oral glucose tolerance test. Subjects will also be
      asked to collect and bring in stool samples at three different time points during the study.

      Subjects will have a 50/50 chance of being assigned to the either study group. This is a
      double-blind study which means neither the study investigator nor the subject will know to
      which group he/she has been assigned. In case of an emergency, the study doctor can get this
      information.
    

Detailed description: 
      Prebiotics are highly effective and important for many applications in medicine. They are not
      absorbed and do not contribute to human nourishment, but rather exert a profound effect on
      the human bowel flora. The principal effect on the human bowel flora is to stimulate the
      growth of Bifidobacterium and Lactobacillus species. These are benign organisms in that they
      are seldom involved in infections or other pathological processes. However, numerous health
      promoting benefits of these bacterial genera have been noted, with effects on infectious and
      non-infectious disease. They induce host genes involved in innate immunity, sometimes in
      collaboration with other elements of the gut flora such as Bacteroides thetaiotaomicron and
      Lactobacillus casei. Animal studies 2 indicate a protective effect against bacterial
      translocation from the GI tract. An extensive cataloguing of genomes of bifidobacteria and
      other intestinal bacteria reveals that the bifids play a very significant role in many
      important areas such as carbohydrate, amino acid, nucleotide, lipid, inorganic ion transport
      and metabolism; energy production and conversion; cell wall and membrane biogenesis; signal
      transduction mechanisms; transcription and translation; and defense mechanisms .

      The metabolic syndrome which includes non-alcoholic fatty liver disease, obesity, and insulin
      resistance has responded to prebiotics in rodent trials; it is estimated that 20-30% of
      populations in developed countries have this disease. Parnell and Reimer have demonstrated
      that prebiotics oligofructose supplementation has the potential to promote weight loss and
      improve glucose regulation in overweight adults likely through suppressed ghrelin and
      enhanced PYY1.

      The investigators have completed a study at UCLA studying the effects of XOS on human
      microbiota. There were three phases including a 2-week run-in period, 8-week intervention
      period, and a 2-week washout. Thirty two volunteers were randomly assigned to take a
      supplement containing 1.4 g XOS (1.4g XOS 70P), 2.8 g XOS (2.8g XOS 70P) or placebo.

      Total of 32 subjects were enrolled into the study. One subject from the placebo group and one
      from the low dose group dropped out of the study for non specific gastrointestinal complaint.

      Altogether, 120 stool samples were received from 11 low dose subjects, 9 high dose subjects,
      and 10 placebo group subjects. Bacterial culture was performed from all the 120 stool samples
      received. One placebo group subject, two high dose group subjects, and two low dose group
      subjects were excluded from the analyses because of compromised specimen quality.

      The Bifidobacterium counts of the subjects after high dose XOS intervention was significantly
      higher from the base line at 4, 8, and 10 weeks. Similarly, the increase of Bifidobacterium
      counts was significantly higher in the high XOS group at 4 weeks compared to the low XOS
      group. The low XOS group had significantly higher Bifidobacterium counts compared to the
      placebo group subjects at 8 and 10 weeks. The total anaerobic flora counts and to some degree
      the total aerobic flora counts of the subjects after high dose XOS intervention were
      significantly higher from the base-line at 4 and 8 weeks. The mean changes of total anaerobic
      flora counts were significantly higher in the high XOS group at 4, 8, and 10 weeks compared
      to the placebo group. Interestingly, also Bacteroides fragilis group counts of the subjects
      after high dose XOS intervention were significantly higher from the base line at 4, 8, and 10
      weeks and the mean changes were significantly higher in the high XOS group compared to the
      low and placebo groups. There were no major significant differences in the counts of
      Lactobacillus sp., Enterobacteriaceae, and clostridia between the three dose groups evaluated

      The XOS was tolerated well by all study subjects (normal adult). At base-line, most of the
      subjects had relatively high counts of Bifidobacterium species with lower counts of
      Lactobacillus species. Several different species of each of these genera were present.
      Bifidobacterium species showed significant increases in counts in subjects on XOS
      supplementation, with the higher dose group showing significantly greater increases than the
      lower dose group. Both high and low dose groups showed significantly higher counts of
      Bifidobacterium sub-species than the placebo group. Lactobacillus species counts did not
      increase significantly in subjects on XOS supplementation. There was a statistically
      significant increase in the counts of the B. fragilis group at all time periods for the high
      dose XOS group. As mentioned before, bifidobacteria may induce host genes involved in innate
      immunity in collaboration with other elements of the gut flora such as B. fragilis group. The
      increase in the counts of the "total anaerobes" reflects the increased counts in the
      Bifidobacterium and B. fragilis group, both of which are anaerobic. Some Bifidobacterium
      species may grow aerobically as well, which may be reflected in the modest increase of the
      aerobic counts in the high dose XOS group. In this study, the XOS supplementation had no
      significant effect on stool pH or SCFAs.

      The investigators propose to conduct a 10 week, randomized, placebo controlled, two arm study
      with 20 subjects with metabolic syndrome. Subjects will be randomly assigned to take a powder
      mixture containing 2.8 g XOS (2.94g XOS 95P) or placebo.
    

Intervention name(s): Sugar Pill; XOS 2.8
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The placebo is identical in appearance to the XOS and contains 505mg maltodextrin; 2.8g XOS is white or off-white crystalline substance and contains 500mg XOS 70P and 20mg maltodextrin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: XOS; pre-diabetic; abnormal glucose levels