Gut microbiota and immunotherapy response

A new meta-analysis links trans-kingdom gut microbiota (bacteria, eukaryotes, viruses, archaea) to immune checkpoint inhibitor (ICI) response in cancer patients. Key species, such as Faecalibacterium prausnitzii and Nemania serpens, predict ICI response and influence immune activity, offering promising biomarkers for personalized immunotherapy. Read more about this under Article 1 below.

Article 1: Effects of gut microbiota on immune checkpoint inhibitors in multi-cancer and as microbial biomarkers for predicting therapeutic response

A meta-analysis shows trans-kingdom gut microbes (bacteria, eukaryotes, viruses, archaea) differ notably between cancer patients who respond to immune checkpoint inhibitors (ICIs) and those who don’t. Species like Faecalibacterium prausnitzii and Nemania serpens, enriched in ICI responders, modulate immune response, offering potential as biomarkers for predicting ICI efficacy in cancer patients. Read the full article here.

In summary: Gut microbes predict immunotherapy response in cancer patients

Article 2: Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses

A comprehensive reanalysis of 9,171 exome datasets from 5,757 rare disease families identified 51 new molecular diagnoses using CNV-detection algorithms. An additional 34 cases revealed partially explanatory pathogenic CNVs. These findings underscore the diagnostic value of revisiting exome sequencing “cold cases” for copy number variants (CNVs) in previously unsolved cases. Read the full article here.

In summary: Reanalysis yields 51 new diagnoses in rare disease cases

Article 3: Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries

Using the extensive gnomAD v4.0 dataset, which includes over 800,000 individuals, researchers estimated gene carrier frequencies (GCFs) for autosomal recessive and X-linked conditions across ancestry groups. Findings highlight more accurate carrier screening for informed reproductive choices, especially in Ashkenazi Jewish populations, with the highest at-risk couple frequency at 6.11%. Read the full article here.

In summary: Expanded genetic data refines carrier screening across ancestries

Article 4: Large-scale pharmacogenomics analysis of patients with cancer within the 100,000 genomes project combining whole-genome sequencing and medical records to inform clinical practice

In the 100,000 Genomes Project, whole-genome sequencing (WGS) of 76,805 participants identified PGx variants linked to drug toxicity in 62.7% of cases. Approximately 14,540 cancer patients annually could benefit from PGx-informed adjustments, particularly with DPYD variants to reduce toxic reactions to capecitabine and fluorouracil. Findings stress the need for diverse PGx data for broader clinical application. Read the full article here.

In summary: Pharmacogenetics guides safer drug dosing in cancer treatments

Article 5: Cardiomyopathies in 100,000 genomes project: interval evaluation improves diagnostic yield and informs strategies for ongoing gene discovery

The 100,000 Genomes Project provided insights into cardiomyopathies in 1,918 participants, showing higher diagnostic yields in pediatric cases (19%) compared to adults (11%). Reanalysis identified new diagnoses in 40% of unsolved pediatric cases, underscoring the value of periodic genome sequencing re-evaluation and improved gene-disease curation to enhance diagnostic accuracy for children with cardiomyopathy. Read the full article here.

In summary: Genomic sequencing boosts pediatric cardiomyopathy diagnostic rates

References

[1] Lin, Y., Xie, M., Lau, H. C.-H., Zeng, R., Zhang, R., Wang, L., Li, Q., Wang, Y., Chen, D., Jiang, L., Damsky, W., & Yu, J. (2025). Effects of gut microbiota on immune checkpoint inhibitors in multi-cancer and as microbial biomarkers for predicting therapeutic response. Med, 6(1), 1–15. https://doi.org/10.1016/j.medj.2024.10.007

[2] Demidov, G., Yaldiz, B., Garcia-Pelaez, J., de Boer, E., Schuermans, N., Van de Vondel, L., Paramonov, I., Johansson, L. F., Musacchia, F., Benetti, E., Bullich, G., Sablauskas, K., Beltran, S., Gilissen, C., Hoischen, A., Ossowski, S., de Voer, R., Lohmann, K., Oliveira, C., Topf, A., … Laurie, S. (2024). Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses. NPJ genomic medicine, 9(1), 49. https://doi.org/10.1038/s41525-024-00436-6

[3] Hotakainen, R., Järvinen, T., Kettunen, K., Anttonen, A. K., & Jakkula, E. (2024). Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries. Genetics in medicine : official journal of the American College of Medical Genetics, 101304. Advance online publication. https://doi.org/10.1016/j.gim.2024.101304

[4] Leong, I. U. S., Cabrera, C. P., Cipriani, V., Ross, P. J., Turner, R. M., Stuckey, A., Sanghvi, S., Pasko, D., Moutsianas, L., Odhams, C. A., Elgar, G. S., Chan, G., Giess, A., Walker, S., Foulger, R. E., Williams, E. M., Daugherty, L. C., Rueda-Martin, A., Rhodes, D. J., Niblock, O., … McDonagh, E. M. (2024). Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, JCO2302761. Advance online publication. https://doi.org/10.1200/JCO.23.02761

[5] Josephs, K. S., Seaby, E. G., May, P., Theotokis, P., Yu, J., Andreou, A., Sinclair, H., Morris-Rosendahl, D., Thomas, E. R. A., Ennis, S., Roberts, A. M., & Ware, J. S. (2024). Cardiomyopathies in 100,000 genomes project: interval evaluation improves diagnostic yield and informs strategies for ongoing gene discovery. Genome medicine, 16(1), 125. https://doi.org/10.1186/s13073-024-01390-9