Unveiling active microbial processes in Earth’s deepest seawater

In situ filtration of hadal seawaters during 12 dives (6–11 km depth) enabled Zhang et al. to perform metagenome-guided metaproteomic analysis of hadal microbiomes. The deepest oceanic ecosystems show...

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Engineering oral commensal nanovaccines to activate mucosal-systemic immune cascades against tumor

Dong et al. develop a bacteria-based oral biohybrid vaccine that induces mucosal immunity and drives a mucosa-periphery-tumor immune cascade. Combined with PD-1 blockade, this strategy enhances effect...

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RNA quality control enables antibiotic tolerance

Nishimoto et al. experimentally evolve bacteria during infection, revealing a ribosomal “crash and reboot” strategy as a mechanism of antibiotic tolerance. Mutations in the RNA degradosome allow RNA t...

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A family of lanthipeptides with anti-phage function

Shomar, Guillaume, et al. report the genomics-driven discovery of a family of more than 2,000 lanthipeptide biosynthetic gene clusters with anti-phage potential. They experimentally demonstrate anti-p...

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Engineering plant-associated microbiome for agriculture

Engineered plant-associated microbiomes provide a transformative approach for sustainable agriculture. In this Forum, we explore five strategies encompassing synthetic community design, native bacteri...

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Hadal topography incubates hidden microbial hotspots in the deepest ocean

Zhao et al. apply integrated multi-omics, geochemical, and fine-scale topographic analyses of sediments across 55 locations in the Mariana Trench to reveal that hadal topography is an overlooked yet i...

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A family of lanthipeptides with anti-phage function

Bacteria produce natural products to adapt to their environments, with phage interactions as major ecological and evolutionary drivers. While some nat…

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A family of lanthipeptides with anti-phage function

Shomar, Guillaume, et al. report the genomics-driven discovery of a family of more than 2,000 lanthipeptide biosynthetic gene clusters with anti-phage potential. They experimentally demonstrate anti-p...

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Exploring functional insights into the human gut microbiome via the structural proteome

Liu et al. develop a structure database of human gut microbial proteins and a structure-aware AI model for remote homolog detection. They demonstrate the power of structure-guided approach in discover...

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Gabija restricts phage circularization and DNA replication

Gabija acts early during phage infection, preventing phage genome circularization and replication. Phage DNA end-binding proteins prevent RecBCD loading onto linear DNA, and the absence of RecBCD lice...

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Cross-kingdom metabolic interactions govern Candida albicans overgrowth and colitis progression

Zhou et al. found that Cladosporium tenuissimum alleviates colitis by inhibiting Candida albicans growth through competition for ornithine. C. albicans can escape this suppression by exploiting threon...

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Following Ariadne’s thread through microbiome-based biomarker discovery in CRC

Colorectal cancer (CRC) carries a microbial fingerprint, but how does it generalize across age, geography, and sequencing platforms? In this issue of Cell Host & Microbe, Pekel and colleagues stitch t...

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Meta-analysis reveals microbiome signatures for colorectal cancer that are universal across age groups and sequencing methods

Pekel, Karcher, et al. present the largest gut microbiome meta-analysis of colorectal cancer to date, integrating 6,779 amplicon and shotgun sequencing profiles. They establish a robust microbiome sig...

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A repair helicase unravels the tangled web of bacterial immunity

DNA repair proteins are repeatedly repurposed for antiviral immunity. In this issue of Cell Host & Microbe, Bell et al. utilized phylogenetic reconstruction of the evolutionary routes of the YprA repa...

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YprA-family helicases provide the missing link between diverse prokaryotic immune systems

YprA-family helicases represent a key hub in the prokaryotic defense network. Through phylogenetic analysis of YprA, Bell and colleagues identify a distinct class of defense systems, called ARMADA. AR...

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Decoding the microbiome: Insights into FMT for depression

While fecal microbiota transplantation (FMT) emerges as a promising microbiome-targeted treatment approach, its application in major depressive disorder (MDD) remains investigational. In this issue of...

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Adjunctive fecal microbiota transplantation for major depressive disorder: A randomized, double-blind, placebo-controlled trial

Li et al. report that adjunctive oral fecal microbiota transplantation provides a rapid and sustained antidepressant response in patients with major depressive disorder. Multi-omics integration reveal...

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Oat-β-glucan potentiates anti-PD-1 efficacy through Faecalibacterium prausnitzii-derived butyrate and indole-3-propionic acid

Yang et al. reveal that oat-β-glucan enhances anti-PD-1 efficacy in colorectal cancer via the F. prausnitzii-butyrate/indole-3-propionic acid (IPA)-CD8+ T cell and dendritic cell axis, which correlate...

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An acidic welcome: How microbial metabolites keep fungi in line

Microbiota-derived metabolites shape gut microbial ecology, but how they limit expansion of potentially pathogenic fungi remains elusive. In this Cell Host & Microbe issue, Mishra et al. and Yasuma-Mi...

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Intracellular acidification by microbiota-derived valeric acid facilitates trans-kingdom ecology limiting Candida parapsilosis colonization

By screening Lachnospiraceae supernatants using SHAP analysis, Yasuma-Mitobe et al. identify bacteria-derived valeric acid (VA) as an inhibitor of C. parapsilosis growth. VA levels inversely correlate...

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Microbiota-derived short-chain fatty acids mediate Candida albicans gastrointestinal colonization resistance

Mishra et al. show that microbiota-derived short-chain fatty acids (SCFAs) inhibit Candida albicans gastrointestinal colonization through two mechanisms: direct fungal inhibition—via intracellular aci...

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Operationalizing microbiome ecology in cancer care

Cancer treatment disrupts the microbiome, worsening outcomes for cancer patients. Ecology frames these changes as transitions between measurable states, enabling the prediction of microbiome trajector...

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Toward precision microbiome therapeutics: From black box to blueprint

The gut microbiome influences human health, yet microbiome-mediated therapies have lagged as metagenomics identifies gut-colonizing microbes without clarifying functional networks. Prior microbiome “r...

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Breaking down barriers to improve phage therapy delivery

Bacteriophage therapy is gaining renewed interest for antimicrobial resistance, but effective delivery remains a major challenge. This review examines current phage therapy practices, barriers to deli...

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Engineering plant-associated microbiome for agriculture

Engineered plant-associated microbiomes provide a transformative approach for sustainable agriculture. In this Forum, we explore five strategies encompassing synthetic community design, native bacteri...

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Mining the code of life for new antibiotics

Antimicrobial resistance is outpacing antibiotic discovery. This review charts the transition from classical environmental screening to digital discovery, where genomes, proteomes, and chemical librar...

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Evolution of antifungal drug resistance: Challenges and mitigations

Antifungal drug resistance is a rising global health concern due to the scarce arsenal of clinically available drugs and the emergence of multidrug-resistant pathogens. Here, we discuss the mechanisms...

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