The microbiome in cancer

A study reveals that Fusobacterium nucleatum subspecies animalis is bifurcated into two distinct clades, and shows that only one of these dominates the colorectal cancer niche, probably through increased colonization of the human gastrointestinal tract.

Efforts to identify microbial signatures of response to immune checkpoint blockade suggest that strain-level associations may be cancer type agnostic but cancer therapy specific.

Multiomic study reveals that tumor microenvironmental factors such as hypoxia influence intracellular infection of Fusobacterium nucleatum in colorectal cancer cells and provides clues to malignant transformation of infected cells.

Understanding the dynamics of the gut microbiota over the course of cancer treatment regimens and their associated adverse events can help identify microbial features that associate with response to immune checkpoint blockade.

Interactions between Peptostreptococcus anaerobius and host cells promote recruitment and activation of myeloid-derived suppressor cells, leading to anti-PD1 immune checkpoint inhibitor resistance and exacerbated colorectal cancer in mice.

A large, publicly available dataset integrating RNA, whole-exome, T cell receptor and 16S rRNA sequencing from patients with colon cancer enables the discovery of a prognostic score consisting of tumor, immune and microbial features.

Poeck and colleagues identify a microbiome signature in patients receiving allogenic stem cell transplantation, which is associated with protective immune-modulatory metabolites, improved survival and less transplant-related mortality.

Modeling contamination sources over multiple samples enhances the analysis of microbiome data.

In patients with advanced melanoma, fecal microbiota transplantation from healthy donors combined with the anti-PD-1 inhibitors nivolumab or pembrolizumab was well tolerated with an encouraging objective response rate of 65% in the first-line treatment setting.

Two products of the anal microbiome improve the specificity and sensitivity of diagnosing high-grade precursor lesions to anal cancer over cytology.

Dietary methionine restriction has been reported to protect from cancer. Ji et al. describe a cancer-promoting effect of methionine restriction mediated by gut microbiota-induced sulfur deficiency and suppression of antitumour immunity.

Statins have anti-cancer effects that are modulated by the gut commensal Lactobacillus reuteri and the tryptophan metabolite, indole-3-lactic acid, in mice and humans.

Metagenomic analysis reveals distinctive multi-kingdom species, functional signatures and bacteria-fungi interactions pattern between excess body weight CRC and lean CRC in gut microbiome, which contribute to precision medicine of CRC.

Transient capsule induction allows engineered bacteria to evade initial immune surveillance in a colorectal cancer model.

Circulating microbiome has been very little studied for blood malignancies. Here, the authors show specific microbiome signatures in the blood are associated with different types of myeloid malignancies and specific genetic mutations.

Anti-cancer fluoropyrimidine drugs have antibacterial effects on the gut microbiome, and these drugs can be metabolized by gut bacteria via conserved pathways also found in mammalian hosts.

A machine learning framework for integrating multi-omic high-dimensional datasets identified disease-specific and shared host gene–microbiome associations across three gastrointestinal diseases.

The role of gut microbiota in acute myeloid leukaemia (AML) remains unclear. Here, the authors show disordered gut microbiota and reduced butyrate cause intestinal barrier damage in AML mice, with increased plasma LPS that accelerates AML progression.

Bacteria from the genus Fusobacterium can promote colorectal cancer (CRC) development; however, the exact Fusobacterium species involved in this process remain underexplored. Here, the authors develop a rpoB amplicon sequencing approach to identify Fusobacterium species and subspecies in CRC patient samples.

The authors show that caloric restriction increases the intestinal abundance of Bifidobacterium bifidum, which in turn blunts tumour development in mice.

Different gut bacteria have been shown to promote colorectal cancer (CRC) progression. The authors identify formate as an oncometabolite derived from Fusobacterium nucleatum, which promotes CRC formation by increasing cancer stemness.

Spatial profiling and single-cell RNA sequencing are used to map the spatial distribution of the microbiota within human tumours, revealing how intratumoral microbial communities contribute to tumour heterogeneity and cancer progression.

Analysis of bacterial, archaeal, fungal and viral species in the gut microbiome of patients with colorectal cancer identified cross-kingdom interactions and multi-kingdom markers of disease.

An analysis of gut microbiomes of patients with non-small-cell lung cancer reveals an association between Bifidobacterium bifidum abundance and response to cancer therapy. In murine models of syngeneic tumours, administration of commercial B. bifidum strains synergizes with immune checkpoint blockade to reduce tumour burden, but the therapeutic potential of B. bifidum is affected by strain-level variation.

In this Review, Pinto and Bhatt provide an overview of DNA-sequencing and RNA-sequencing approaches that can be used to study the composition, structure, and function of microbiomes and discuss the biological insights they provide.

The gut microbiota has been implicated in the increasing prevalence of thyroid disorders, including autoimmune thyroid diseases and thyroid cancers, through its effects on gut integrity, immune regulation and thyroid hormone metabolism, as outlined in this article.

In this Review, Crawford and Turocy examine diverse small molecule metabolites produced by the human microbiota, their role as potential risk factors for cancer development as well as novel mechanistic insights demonstrating their association with gastrointestinal cancer.

In this Perspective article, Mel Greaves and co-workers outline emerging evidence that suggests that children with newly diagnosed acute lymphoblastic leukaemia may have a delayed maturation of the gut microbiome compared with healthy children, a deficit that might be associated with early-life epidemiological factors and could contribute to the risk of transformation of preleukaemic clones in response to common infectious triggers.

The role of the microbiota in tumorigenesis has garnered considerable attention over the past two decades. In this Review, El Tekle and Garrett explore the current and evolving understanding of microbiota in cancers of various internal organs, as well as highlighting opportunities for targeting bacteria for cancer prevention, diagnostics and treatment.

Emerging data indicate a central role for the microbiota in all aspects of colorectal cancer (CRC). Despite this general consensus, understanding the role of specific components of the microbiota in such a way that enables the development of clinical interventions or tools to inform clinical decision-making has thus far proved challenging. In this Review, the authors summarize the role of the microbiota in CRC, including in prevention, in interactions with treatment and as a source of novel biomarkers.

Many studies attempting to identify biomarkers for predicting of immune-checkpoint inhibitor (ICI) efficacy have led to the description of Gut OncoMicrobiome Signatures (GOMS). Several GOMS support an association between oncogenesis and intestinal dysbiosis, and other GOMS are shared between patients with several cancer subtypes and individuals with seemingly unrelated chronic inflammatory disorders. The authors of this Review discuss these patterns as well as the findings from a meta-analysis of GOMS associated with clinical benefit from ICIs, and propose practical guidelines to incorporate GOMS in decision-making in immuno-oncology.

Advances over the past decade have established a prominent role of the gut microbiota in the modulation of immune homeostasis and function, including in patients with cancer receiving immune-checkpoint inhibitors. In this Review, the authors summarize current knowledge of the role of the microbiota in this context, describe several methods of modulating the microbiota clinically to improve patient outcomes, and highlight important future directions in this expanding area of research.

The importance of commensal fungi in health and disease is becoming increasingly clear. In this Review, Ost and Round discuss the involvement of the mycobiota in intestinal diseases, and consider potential opportunities to target fungi and their interactions for therapeutic purposes.

This Review outlines the mechanisms by which the microbiota alters the efficacy and immunotoxicity of established and emerging cancer treatments, and discusses the benefits and limitations of microbiota-targeting interventions that are being investigated to improve patient outcomes.

Sears and colleagues discuss the latest advances in the understanding of host and microbiota mechanisms involved in the relationship between the microbiome and cancer and emerging avenues for applying these insights to cancer therapy.

The role of the gut microbiome in human health and disease is being increasingly recognized. This Review discusses microbiome engineering strategies to treat the dysbiosis of the gut microbiota, which has been linked to the pathogenesis of multiple human diseases.

The human microbiome plays a central role in health and disease. This Review discusses the design of human organ-on-a-chip platforms to model host–microbiome interactions in vitro and investigate microbiome-associated diseases as well as microbiome-mediated interventions.

In this Review, White and Sears examine recent evidence showing the link between the gut microbiota and colorectal cancer (CRC) and discuss the roles and mechanisms of specific microorganisms as well as of complex microbial communities in the pathogenesis of CRC.

Archaea are an overlooked member of the human gut microbiota. This Perspective discusses key characteristics of archaea, their role in human health and physiology, and the clinical relevance of methanogenic archaea in the human gastrointestinal tract.

The gut microbiota has been shown to regulate responses to various cancer therapies, and the microbial species involved and their underlying mechanisms have begun to be unravelled. In this Perspective, Fernandes and colleagues present this evidence and then outline how it could be used to develop microbiota-based therapies for patients with cancer.

Microbiome epidemiology associates microbial community features with health outcomes, traits or exposures in human host populations. In this Review, the authors discuss ways in which various microbiome features at varying levels of resolution (community, strain, pathway or gene) influence human health using established examples of microbiome-associated changes linked with host outcomes.

This Review presents evidence that points to a critical role for metabolic pathways in influencing processes that support the early stages of tumour development, provides examples of the role of metabolic networks intrinsic to cancer cells in tumour progression and outlines how environmental factors can affect tumour incidence.

 People from minority racial and ethnic groups continue to experience disproportionate cancer incidences and cancer-associated mortality rates. In this Comment, Byrd and Wolf explore the contribution of non-medical factors to the composition of the gut microbiome, and how this may be an actionable target for reducing these disparities.

The composition of the gut microbiota has emerged as a tumour-extrinsic factor that modulates response to immune-checkpoint inhibitors (ICIs), although the lack of consistency in microbiota signatures across studies has limited their value as reliable biomarkers. Herein, we discuss a recent study in which longitudinal microbiome profiling identified several taxa that are persistently enriched in patients with melanoma and a favourable response to ICIs.

Harnessing the potential of microbiota analysis creates new opportunities in diagnosing diseases, improving treatment efficacy, reducing treatment complications and preventing disease recurrence. However, microbiota analysis has not yet been integrated into clinical management workflows. Here, we discuss crucial characteristics of microbiota analysis systems for clinical translation.

Live microorganisms can be manipulated and engineered for colorectal cancer detection and treatment through methods such as faecal microbiota transplantation, native bacteria engineering and synthetic circuit engineering. Although promising, substantial effort is required to translate these approaches for clinical use.

Fu et al. provide data indicating a pathogenic role for Streptococcus anginosus in gastric cancer.

In this Viewpoint article, we asked three scientists working on the cancer mycobiome to provide their opinions on advancements and challenges and what the future holds for this exciting field of cancer research.

Tumors are rife with bacteria and fungi. Their ubiquity is proving useful in detecting cancers, categorizing them, and even determining whether certain interventions will work.

New light is being shed on the interactions between the gut microbiome, cancer cell signalling and the host immune response. With this knowledge, microbiota-based approaches for improving cancer prevention, prognostication and therapy have started to materialize and will contribute to reducing the global cancer burden.

The burgeoning field of intratumoural microbiome research has been driven by advances in next-generation sequencing technologies, with compelling evidence on the role of the microbiota in cancer initiation, progression and patient response to treatment. Here, we discuss new concepts of the tumour-associated microbiota and what is needed to advance the translational impact of these findings in gastrointestinal cancers.

Two recent large-cohort studies reinforce the potential predictive capability of gut microbiota for immune-checkpoint inhibitor response and toxicities in patients with melanoma. However, additional investigations are required to understand the mechanistic underpinnings of this complex multifaceted relationship, and how it can be exploited for personalized cancer care.

Luo et al. uncover strong associations between the tumour microbiome and race, a finding that further emphasises the need for race diversity in cancer studies.

Despite the profound clinical success of immune-checkpoint inhibitors, their effectiveness is limited by intrinsic and acquired resistance. Bullman, Zitvogel and colleagues provide their views on two clinical trials modulating the microbiome of immunotherapy-resistant patients with melanoma via transplantation of fecal microbiota from patients who responded to immunotherapy.