Modern molecular techniques have progressed to the point where sequencing can seem almost quaint. At the Basic Science Symposium of The Liver Meeting 2022, new techniques were on full display, with sessions devoted to epigenetics, microbiome analysis and spatial transcriptomics. But the first session was still on genetic variants in all their forms – rare variants, common variants and non-germline mutations.

High hopes rest on manipulating the gut microbiome in order to treat a multitude of disorders. Clinical validation for the idea has come from the success of fecal microbiome transplants to treat chronic Clostridium difficile infections. Such transplants are in clinical trials to treat other gastrointestinal disorders, and more targeted methods to manipulate the microbiome are being developed as well, not just for infections, but in a multitude of other indications. Targeting the gut microbiome may turn into a way to alleviate inflammatory bowel disease, food allergies, and even psychiatric conditions.

Saniona AB has completed preclinical development with SAN-903 and is ready to start the regulatory process for entering phase I trials either alone or together with a partner. SAN-903 is a novel, potential first-in-class medicine based on inhibition of the calcium-activated potassium ion channel KCa3.1.

Equillium Inc. has advanced EQ-102, a first-in-class multi-cytokine inhibitor of IL-15 and IL-21 for celiac disease, into a phase I study in healthy volunteers.

The simultaneous mapping of DNA mutations and epigenetic changes as colorectal cancer evolves has for the first time tracked their relative contributions and shown epigenetic control of gene transcription is far more important than somatic mutations in enabling tumors to adapt and develop a survival advantage over other cells. In an analysis of 1,373 samples from 30 colorectal cancer samples, epigenetic changes were highly common in cells that had become cancerous and occurred around known cancer driver mutations. These epigenetic alterations were heritable, were passed on at each cell division, and in addition to a direct contribution to the evolution of tumors also influenced how cancer cells accumulated DNA mutations. The modifications to gene regulation conferred survival advantages that meant cancer cells grew faster than normal counterparts. While it is not news that epigenetic changes are involved in tumor development, previously it was not clear what the relative contribution was, and that their effect could be independent of DNA mutations.

Peking University researchers in collaboration with the NIH have discovered a new biochemical pathway related to a bacterium that eliminates nicotine in the intestine. The findings could lead to new ways to improve nonalcoholic fatty liver disease in smokers.