Gut Microbiome Studies Link Bacterial Composition to Health Outcomes and Genetic Factors

A large international study led by researchers at the University of Cambridge has identified a little-known group of gut bacteria that appears far more often in healthy people. The group, called CAG-170, was consistently found at higher levels in individuals without chronic illness.

Using advanced computational techniques, the team searched for CAG-170's genetic fingerprint in gut microbiome samples from more than 11,000 people across 39 countries. Healthy individuals had more of these bacteria than people with conditions such as inflammatory bowel disease, obesity, and chronic fatigue syndrome. The dataset included healthy individuals as well as people diagnosed with 13 different diseases, including Crohn's disease, colorectal cancer, Parkinson's disease, and multiple sclerosis.

CAG-170 is known only through its genetic signature. Scientists have not been able to grow most of these bacteria in the lab, which has made them difficult to study directly. Further genetic analysis showed that CAG-170 has the ability to produce large amounts of Vitamin B12. It also carries enzymes that help break down carbohydrates, sugars, and fibers in the gut.

Researchers believe the Vitamin B12 produced by CAG-170 likely supports other beneficial gut bacteria rather than directly benefiting the person hosting it. In other words, these microbes may help maintain balance within the broader gut ecosystem. The study was published in the journal Cell Host & Microbe.

In a second analysis, the scientists examined the full gut microbiome composition of more than 6,000 healthy individuals to identify which species appeared most capable of stabilizing the gut ecosystem. Once again, CAG-170 ranked as the group most consistently linked to health. A third analysis focused on people with dysbiosis, a condition in which the gut microbiome becomes imbalanced. Lower levels of CAG-170 were associated with a greater likelihood of dysbiosis.

This research builds on earlier effort to assemble a detailed reference library of microbial genomes found in the human gut. That resource, known as the 'Unified Human Gastrointestinal Genome catalogue', maps the genetic blueprints of microbes that live inside us. The work identified more than 4,600 bacterial species living in the gut. Remarkably, more than 3,000 of these had never been documented there before, highlighting how much of the microbiome remains unexplored.

In a separate study investigating orthopedic recovery, stool samples were collected from postmenopausal women at preoperative baseline and 6 weeks postoperative time points. Microbial profiling was performed using 16S rRNA gene sequencing on the Illumina MiSeq platform, and data processing and taxonomic analysis were conducted using QIIME2. The results revealed significant temporal shifts in gut microbial composition during the recovery period.

Bacterial diversity varied across time points, with Firmicutes and Bacteroidetes identified as the dominant phyla. Increased abundance of these taxa was strongly associated with improved functional outcomes and faster recovery. In contrast, elevated levels of Proteobacteria and Escherichia were linked to delayed healing and poorer clinical performance. The predictive model achieved an accuracy of 85%, demonstrating the robustness of gut microbiome signatures as indicators of postoperative recovery.

Meanwhile, the largest genome-wide association study (GWAS) to date looking at links between human genetics and microbial species found in the gut has identified and replicated 11 genetic variants shaping the composition of the gut microbiome, nine of which have been reported for the first time. Two back-to-back studies, published in Nature Genetics, highlight the role genes involved in gut physiology can play in shaping the gut microbiome.

Researchers analyzed genetic data and gut bacteria from over 16,000 adults across four Swedish population-based studies. This led them to identify a total of 15 genetic variants across eight genes that were significantly associated with 14 common bacterial species. A replication study conducted in a Norwegian cohort of more than 12,000 people confirmed the initial findings for 11 genetic variants across six genes.

Two of the genes identified had already been reported and replicated in previous GWAS studies. These were the LCT gene encoding for the lactase enzyme, which breaks down lactose during digestion, and the ABO gene, which encodes for a glycosyltransferase enzyme that determines the oligosaccharides present on the cell surface.

Among the nine newly found genetic variants were genes encoding sensors for fatty acids produced by the microbiota, genes involved in bile acid metabolism and variants that determine the composition of the mucosal layer that lines the gut. Some of these genetic variants were linked to the risk of gluten intolerance, hemorrhoids and cardiovascular diseases, suggesting that changes in the composition of intestinal bacteria could provide a way to better understand how genetic risks affect health.