Gastrointestinal microbiome association with health status in Latvian population reveals significant shifts in gastrointestinal cancer patients at taxonomical and functional level

Due to the close physiological relationship between humans and their inhabiting microorganisms, many diseases are believed to be associated with alterations from a “healthy” gut microbiome, however, there is still a lack of understanding to generalize this knowledge.

We conducted a study in the Latvian population to determine the association of the faecal microbiome with health, disease, and death. To do this, we obtained stool samples from 30 patients in each disease group, e.g., autoimmune, hepatitis, cardiovascular, colorectal cancer, and patients who passed away within five years of sampling. An additional 60 stool samples were collected from generally healthy individuals and served as controls. All samples were analysed using shotgun sequencing methodology employing DNBSEQ-G400RS sequencing platform (MGI Ltd, China). Taxonomical classification was assigned with MetaCache v.2.3.1 and NCBI RefSeq v.210 database, while functional annotation and annotation of antimicrobial resistance genes were performed with PROKKA v.1.14.6 and RGI v.5.1.1, respectively, using the UniProtKB and CARD reference databases.

Metagenomic analysis revealed the most significant differences between the control and colorectal cancer groups, showing differences at both the taxonomic and functional levels. Compared with the control group, a considerable number of taxa were significantly more abundant (n = 201) in the faecal metagenome of colorectal cancer group, e.g., some bacterial species that have been associated with human infections, such as Parvimonas micra (p < 0.001), Gemella morbillorum (p < 0.001) and Fusobacterium nucleatum (p < 0.001). Furthermore, the cancer group had a significant decrease in the abundance of various taxa (n = 210), including several beneficial bacteria from the genus Bifidobacterium (e.g., B.adolescentis, B.catenulatum, B.angulatum, B.bifidum (for all p < 0.05) and other species, such as Bacillus spizizenii (p < 0.001), Mesorhizobium terrae (p < 0.001), and Ligilactobacillus ruminis (p=0.002). Functional analysis revealed that the faecal metagenome of patients is represented by several antibiotic resistance genes, most of which act against drug classes such as glycopeptides, nitroimidazoles and tetracyclines. Comparing other disease groups to control, few bacterial entities were enriched/depleted in cardiovascular group, whereas no significant associations were detected for autoimmune and hepatitis patients.

Therefore, the results of our study demonstrate major deviations in the gastrointestinal microbiome of individuals with colorectal cancer, and provides direction for further research into the role of microorganisms and functional pathways in this disease. Such research may lead to the development of novel supportive treatments targeting the gastrointestinal microbiome, improving both the prognosis and quality of life for colorectal cancer patients.

The authors.

ERDF1.1.1.2/VIAA/3/19/460 "Association of human intestinal and blood microbiome composition with general state of health and mortality within population of Latvia".

All authors have declared no conflicts of interest.