GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota...

Area of Science:

• Microbiology
• Bioinformatics
• Genomics

Background:

• Current gut microbiome analysis relies on species/gene identification, limiting functional and diversity insights.
• Calculating ecological similarity from whole genome shotgun (WGS) metagenomic data is challenging.
• Existing methods lack direct calculation of microbiome similarity from WGS sequences.

Purpose of the Study:

• To develop and validate an alignment-free method for calculating microbiome similarity directly from WGS metagenomic sequences.
• To apply this method to assess developmental changes in infant gut microbiomes.
• To quantify donor microbiota engraftment in fecal microbiota transplantation (FMT) studies.

Main Methods:

• Implemented an alignment-free method analogous to the Bray-Curtis index for species.
• Developed the General Utility for Testing Sequence Similarity (GUTSS) software.
• Applied GUTSS to analyze infant gut microbiome development and FMT engraftment in Crohn's disease patients.

Main Results:

• Demonstrated a novel method for calculating WGS metagenomic sequence similarity.
• Measured developmental shifts in infant intestinal microbiomes over the first 3 years of life.
• Quantified donor microbiome engraftment in FMT recipients and developed a relative index of similarity to the donor.

Conclusions:

• The developed method enables quantification of gut microbiome changes independent of species identification and database bias.
• This approach is sensitive to alterations in microbial relative abundance, crucial for evaluating FMT efficacy.
• The method can be formulated as an index to correlate engraftment success with clinical outcomes and guide microbiome-targeted therapies.