What is already known
Gut microbes have been linked to a plethora of diseases, including colorectal cancer, inflammatory bowel disease and irritable bowel syndrome. The dysregulation of host gene expression has also been implicated in these conditions. However, how the gut microbiota may couple with dysregulation of host gene expression remains unclear.
What this research adds
Researchers developed a machine-learning platform to analyze both gene-expression patterns and gut microbiotas from dozens of colon samples from people with colorectal cancer, inflammatory bowel disease and irritable bowel syndrome. They found that, , regardless of the disease, specific gut microbes are associated with common pathways implicated in gastrointestinal inflammation, gut barrier protection and energy metabolism.
Conclusions
The findings suggest that similar microbes can influence human health through the regulation of different host genes.
Gut microbes have been linked to a plethora of diseases, including colorectal cancer, inflammatory bowel disease and irritable bowel syndrome. New research reveals that specific gut microbes are associated with common disease pathways.
The findings, published in Nature Microbiology, suggest that similar microbes can influence human health through the regulation of different host genes. “Our results represent an important step towards characterizing the association between gut microbiome and host gene regulation, and understanding the contribution of the microbiome to disease etiology,” the researchers say.
Previous research has associated the abundance of bacteria such as Peptostreptococcaceae and Streptococcus with colorectal cancer, inflammatory bowel disease and irritable bowel syndrome. The dysregulation of host gene expression has also been implicated in these conditions. For example, the disruption of Notch and WNT signaling pathways has been linked to colorectal cancer, and altered immune response and intestinal antibacterial gene expression have been associated with irritable bowel syndrome. However, how the gut microbiota may couple with dysregulation of host gene expression remains unclear.
To characterize the interplay between microbes and host genes, researchers led by Ran Blekhman at the University of Minnesota developed a machine-learning platform to analyze both gene-expression patterns and gut microbiotas from dozens of colon samples from people with colorectal cancer, inflammatory bowel disease and irritable bowel syndrome.
Common pathways
The researchers found that, regardless of the disease, specific gut microbes are associated with common pathways implicated in gastrointestinal inflammation, gut barrier protection and energy metabolism.
In the RAC1 pathway, which regulates mucosal repair and immune response in the gut, host gene expression was associated with microbiota composition, with overlapping genes in all three conditions. However, specific microbes correlated with each disease. In colorectal cancer, for example, the RAC1 pathway was associated with oral bacteria such as Streptococcus and Synergistales. In inflammatory bowel disease, this pathway was linked to microbes including Granulicatella and Clostridium. In irritable bowel syndrome, it was associated with Bacteroides massiliensis, Bifidobacterium and Odoribacter.
The team also found unique host pathways for which gene expression correlated with gut microbes only in one of the three diseases. For example, the Syndecan-1 pathway, which is thought to regulate the activity of cancer cells, was associated with gut microbes only in colorectal cancer. This pathway was linked to Parvimonas and Bacteroides fragilis — two microbes that are known to promote intestinal cancer.
“The disease-specific pattern of host gene–microbe crosstalk suggests that gut microbes, either through direct interaction with host cells or through indirect interaction (for example, via production of specific metabolites), may regulate host gene expression differently in specific disease contexts,” the researchers say.
Different interactions
Some microbes involved in inflammatory conditions produced different effects based on their interaction with different host genes and through different pathways, the team found. For example, Streptococcus was associated with genes that regulate inflammatory pathways in colorectal cancer, but it correlated with host genes that modulate macrophage inflammatory response in inflammatory bowel disease and irritable bowel syndrome.
“Although diseases can be characterized by similar microbial perturbations, these microbes can impact disease-specific pathophysiological processes through association with different host genes in each disease,” the researchers say.
The machine-learning approach developed in this study could be applied to other conditions for identifying host gene-microbiota interactions that may influence clinical outcomes, they add.
