Ginger and Gut Microbiome (GINGER)

This is a pilot trial to evaluate the feasibility of conducting a large randomized trial and
estimate the effects of ginger extract on the gut microbiome. The pilot study will recruit
from multiple sites 95-100 subjects aged 50-75 years old who were diagnosed with colorectal
adenoma within the last five years. There will be 47-50 subjects in the treatment group and
47-50 in the placebo group. The subjects will be randomized to receive either 2000 mg of
ginger extract per day (1000 mg twice a day) or matching placebo.

Subjects will provide three stool specimens for analysis of the intestinal microbiome over a
12-week period at the following intervals: Week 0 (Day 1), Week 6, and Week 12. Although the
gut microbiome is stable within a period of 1-2 months, a control arm will be included to
account for potential dietary and other changes that may affect the gut microbiome. Gut
microbiome composition - the presence, abundance, and diversity of bacterial taxa - will be
derived by sequencing microbial 16S ribosomal RNA genes.

Primary Aims:

Aim 1 is to estimate the impact of a 6-week daily intake of 2000 mg of ginger extract on the
composition of the gut microbiome using a randomized placebo-controlled double-blinded
design, i.e. examine the change of microbiome over time within and between the subjects.

Aim 2 will examine the correlation between the ginger-related changes in microbiome profile
with the levels of circulating biomarkers: urinary Prostaglandin E (PGE) metabolites.

Hypothesis: In the ginger versus placebo arm, gut microbiome will shift towards a lower
proportion of pro-inflammatory, bacteria associated with colorectal cancer (CRC) and higher
proportion of anti-inflammatory, CRC-protective bacteria.

Secondary Aim:

1. At the end of the study, we expect to show that ginger decreases the relative abundance
of pro-inflammatory, CRC-predisposing taxa and increases the abundance of
anti-inflammatory, CRC-protective taxa, i.e., demonstrate that ginger boosts changes in
gut microbiome that are protective against CRC, as well as assess ginger-induced changes
in immune response.

2. The similarities of bacterial profiles will be compared between three time points
baseline and 6 Weeks and 12 Weeks to estimate whether 6-week is a sufficient time for
washout.

Inclusion Criteria:

- Colorectal adenoma diagnosis

Exclusion Criteria:

- Allergy or sensitivity to ginger

- Active cancer

- Unstable medical condition

- Unstable diet or weight