This Perspective reflects on advances made in the field of human gut microbiome-derived biotherapeutics, from faecal microbiota products to rationally designed second- and third-generation live biotherapeutics, and discusses the future of this developing field.

Chemla et al. review the release of bacteria into the environment and propose engineering strategies to help improve performance and reduce risk.

Biochemical characterization of 66 carbohydrate-active enzymes from the gut microorganism Akkermansia muciniphila reveals that these enzymes can break down a range of host glycans, including mucin, which they degrade to completion.

Samples from over 4,000 bats representing 40 different species yield 8,176 viral metagenomes that expand RNA virus diversity and decipher environmental and anthropogenic factors influencing bat viral ecology.

Tecovirimat forces dimerization of the poxvirus phospholipase F13 blocking virus spread. Clinical monkeypox virus strains resistant to tecovirimat show mutations in the F13 dimer interface.

In a randomized controlled trial, the effect of sulforaphane (provided as a broccoli sprout extract) on fasting blood glucose in individuals with prediabetes was tested, in the context of gut microbiota composition and function.

Quantitative flow virometry assay to measure the shape of viral particles under various conditions reveals that influenza virus infections dynamically tune shape distribution of progeny particles depending on viral efficiency.

Hexa-acylated lipopolysaccharides from the gut microbiota are associated with efficacy in patients with cancer receiving anti-PD-1 and stimulate host immune activation for enhanced anti-tumour immunity in mouse models.

Metabolic engineering guided by laboratory evolution enables upcycling of nylon by Pseudomonas putida.

HD5 induces filopodial extensions in epithelial cells that the pathogen Shigella exploits to facilitate invasion and infection.

Determining whether human organs house a resident microbiome is challenging and the findings can be controversial. However, forging collaborations and careful study design can help overcome these issues.

Microbiome science is a multi-disciplinary field, but classical microbiologists are needed to ensure advances are grounded in our understanding of basic microbiological concepts.

Global food insecurity is a growing crisis, but microbes could offer an effective tool for sustainable agriculture.

The Oropouche virus has long been overlooked, but following a recent global expansion the virologist Marta Giovanetti argues for a One Health strategy to address this emergent public health threat.

We look back at this year’s Nature Microbiology content covering the spectrum of microbiology, from fundamental advances to those that aim to tackle pressing concerns facing human health, the environment and the climate.