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  1. Philip J Smith
  1. Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  1. Correspondence to Dr Philip J Smith, Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Philip.Smith{at}liverpoolft.nhs.uk

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Basic science

Faecal microbiota transplant promotes therapeutic response in patients with melanoma

Baruch E, Youngster I, Ben-Betzale G, et al. Faecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 2020. doi: 10.1126/science.abb5920.

Mechanisms to overcome resistance to antiprogrammed death-1 (anti-PD-1) therapies are lacking. The gut microbiome has been shown to influence the response of tumours to anti-PD-1 immunotherapy in pre-clinical mouse models and observational patient cohorts. In this phase I clinical trial, Baruch et al assessed the safety and feasibility of faecal microbiota transplantation (FMT) in overcoming anti-PD-1 resistance in metastatic melanoma (MM). The trial included 10 patients with cancer, who underwent microbiome depletion with orally ingested antibiotics prior to FMT. Donors had been successfully treated with anti-PD-1 monotherapy for MM and achieved a complete response (CR) for at least 1 year (n=2). Patient’s FMT were performed via both colonoscopy and administration of oral stool capsules followed by reinitiation of anti-PD-1 therapy. Clinical response, defined by regression of tumour size, was observed in 3 of 10 patients, inclusive of two partial responses and one CR. All three had received FMT from the same donor; however, authors note that the study was statistically powered to assess safety and not to compare efficiency between donors. This result mirrors the inconsistency among previous observational reports in pinpointing specific ‘response-inducer’ microbiota characteristics. FMT was associated with favourable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumour microenvironment. The trial concluded that FMT from CR donors and reinitiation of anti-PD-1 therapy in patients with refractory MM were safe and feasible. These findings support the growing body of evidence that modulating the gut microbiome may be a viable therapeutic avenue to overcome anti-PD-1 resistance in cancer.

Rotavirus uses paracrine signaling to cause diarrhoea

Chang-Graham A, Perry J, Engevik M, et al. Rotavirus induces intercellular calcium waves through ADP signaling. Science 2020;370:eabc3621. doi: 10.1126/science.abc3621.

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.