A mouth bacteria has starring role in colorectal cancer: study

Subject: Science and tech

Sec: Health

Context:

Recent research by the Fred Hutchinson Cancer Center in the U.S. has discovered a specific subtype of the bacterium ‘Fusobacterium nucleatum’ that is more prevalent in colorectal cancer (CRC) tumours.

Details:

This subtype’s genetic characteristics may enhance its association with gut cancers.
In experiments, mice infected with this subtype developed precancerous intestinal growths known as adenomas.
These findings, pointing to a potential role of Fusobacterium in CRC progression, could lead to new diagnostic and treatment strategies for CRC, which is increasingly prevalent globally and notably among younger populations.
- CRC is the seventh most common type of cancer in India, where the number of cases rose by 20% from 2004 to 2014. Worldwide, the overall CRC incidence has declined but the incidence of age-adjusted early-onset CRC “has risen at an alarming rate of 2-4% in many countries, with even sharper increases in individuals younger than 30 years.”

About Fusobacterium nucleatum:

Fusobacterium nucleatum, typically found in the human mouth, has been linked to colorectal cancer (CRC) by promoting cancer cell evasion from the immune system.
Researchers cultured Fusobacterium bacteria from 130 human colorectal cancer (CRC) tumours and conducted a full genetic analysis.
They discovered that among the four known subspecies of Fusobacterium nucleatum, only Fusobacterium nucleatumanimalis (Fna) was significantly linked to CRC tumours.
Pangenomic analysis, which maps all genes of a species including its accessory genome (genes not shared by all members), showed that Fna has a notably small core genome, suggesting diverse subtypes within Fna.
Further genetic tracing revealed that Fna consists of two distinct evolutionary lineages, referred to as clades.
These clades, named Fna C1 and Fna C2, were examined, with Fna C2 found to be significantly associated with CRC tumours and possessing additional genetic features that may enhance this association.
This differentiation into clades highlights the complex relationship between Fusobacterium nucleatum subtypes and their role in colorectal cancer.

Colonising the gut:

The study identified physical and genetic distinctions between two clades of Fusobacterium nucleatumanimalis (Fna) which contribute to their association with colorectal cancer (CRC) tumors.
The Fna C2 bacteria, physically longer and thinner than Fna C1, possess unique genes enabling them to utilize ethanolamine and 1,2-propanediol for energy in the gut, traits not found in Fna C1. This enhanced metabolic capability likely aids their survival and association with CRC tumours.
Further evidence of Fna C2’s adaptation to the gut environment was found in an analysis of over 1,200 human stool samples, where genes necessary for metabolizing these compounds were more prevalent in samples from CRC patients compared to healthy individuals.
The study also proposed a new pathway for these bacteria to travel from the mouth to the gut, suggesting they can survive the journey through the highly acidic stomach environment, unlike other bacteria.
Fna C2 has evolved acid-resistant genes that activate in acidic conditions, enabling their survival and colonisation in the gut, contrasting with the previously assumed route of bloodstream infection during oral injuries or procedures.

Impact of the Fusobacterium nucleatumanimalis (Fna) C2 bacteria:

The research investigated the impact of Fusobacterium nucleatumanimalis (Fna) C2 bacteria on tumour development by introducing them into the inflamed guts of mice, which led to a higher incidence of adenomas compared to mice treated with Fna C1.
The metabolic profiles of Fna C2-treated mice also indicated changes that support tumour progression, affirming Fna C2‘s unique ability to alter the intestinal environment in ways conducive to colorectal cancer (CRC).
Further validation in human patients showed that Fna C2 was predominantly found in CRC tissues and stool samples of CRC patients, but not in non-cancerous samples or those from healthy individuals. This specificity suggests potential for Fna C2 as a marker for CRC detection.
Experts see the study as a promising step towards microbial cellular therapies for cancer and targeted microbial interventions for CRC.
The findings encourage future research into tracking microbial changes in high-risk individuals to better understand the interactions between specific bacterial strains and cancer development.
Challenges remain, including the development of treatments that can selectively target harmful bacteria like Fna C2 without disrupting other beneficial gut bacteria.

Source: TH