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As plant-based diets gain traction, interest in their impacts on the gut microbiome is growing. However, little is known about diet-pattern-specific metagenomic profiles across populations. Here we considered 21,561 individuals spanning 5 independent, multinational, human cohorts to map how differences in diet pattern (omnivore, vegetarian and vegan) are reflected in gut microbiomes. Microbial profiles distinguished these common diet patterns well (mean AUC = 0.85). Red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes (for example, Ruminococcus torques, Bilophila wadsworthia and Alistipes putredinis) negatively correlated with host cardiometabolic health. Conversely, vegan signature microbes were correlated with favourable cardiometabolic markers and were enriched in omnivores consuming more plant-based foods. Diet-specific gut microbes partially overlapped with food microbiomes, especially with dairy microbes, for example, Streptococcus thermophilus, and typical soil microbes in vegans. The signatures of common western diet patterns can support future nutritional interventions and epidemiology., Competing Interests: Competing interests: T.D.S. and J.W. are co-founders of ZOE Ltd. F.A., S.E.B., T.D.S. and N.S. are consultants to ZOE Ltd. A.A., E.B., A.C.C, L.F., J.C.P., R.D., J.W. and K.M.B. are or have been employees of Zoe Ltd. A.A., J.C.P., R.D., J.W., A.C.C, K.M.B., S.E.B., T.D.S., F.A. and N.S. receive options in ZOE Ltd. All other authors declare no competing interests., (© 2025. The Author(s).)

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components. Here we conducted a multi-cohort, multi-omic analysis of US and UK populations with detailed dietary information from a total of 22,867 participants, which we then integrated with public data from 211 cohorts (N = 54,198). The link between coffee consumption and microbiome was highly reproducible across different populations (area under the curve of 0.89), largely driven by the presence and abundance of the species Lawsonibacter asaccharolyticus. Using in vitro experiments, we show that coffee can stimulate growth of L. asaccharolyticus. Plasma metabolomics on 438 samples identified several metabolites enriched among coffee consumers, with quinic acid and its potential derivatives associated with coffee and L. asaccharolyticus. This study reveals a metabolic link between a specific gut microorganism and a specific food item, providing a framework for the understanding of microbial dietary responses at the biochemical level., Competing Interests: Competing interests: G.H., J.W. and T.D.S. are co-founders of ZOE. G.H., J.W., R.D., F.G. and K.M.B. are or have been employees of ZOE. N.S., F.A., S.E.B., C.H. and T.D.S. are consultants to ZOE. T.D.S., R.D., J.W., G.H., F.A., N.S. and S.E.B. receive options with ZOE. All other authors declare no competing interests., (© 2024. The Author(s).)

The resident microbiome in food industries may impact on food quality and safety. In particular, microbes residing on surfaces in dairy industries may actively participate in cheese fermentation and ripening and contribute to the typical flavor and texture. In this work, we carried out an extensive microbiome mapping in 73 cheese-making industries producing different types of cheeses (fresh, medium and long ripened) and located in 4 European countries. We sequenced and analyzed metagenomes from cheese samples, raw materials and environmental swabs collected from both food contact and non-food contact surfaces, as well as operators' hands and aprons. Dairy plants were shown to harbor a very complex microbiome, characterized by high prevalence of genes potentially involved in flavor development, probiotic activities, and resistance to gastro-intestinal transit, suggesting that these microbes may potentially be transferred to the human gut microbiome. More than 6100 high-quality Metagenome Assembled Genomes (MAGs) were reconstructed, including MAGs from several Lactic Acid Bacteria species and putative new species. Although microbial pathogens were not prevalent, we found several MAGs harboring genes related to antibiotic resistance, highlighting that dairy industry surfaces represent a potential hotspot for antimicrobial resistance (AR) spreading along the food chain. Finally, we identified facility-specific strains that can represent clear microbial signatures of different cheesemaking facilities, suggesting an interesting potential of microbiome tracking for the traceability of cheese origin., (© 2024. The Author(s).)

Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals 1 , is enriched in human colorectal cancer (CRC) tumours 2-5 . High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis 5-8 . Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche., (© 2024. The Author(s).)

Malignant bile duct obstruction is typically treated by biliary stenting, which however increases the risk of bacterial infections. Here, we analyzed the microbial content of the biliary stents from 56 patients finding widespread microbial colonization. Seventeen of 36 prevalent stent species are common oral microbiome members, associate with disease conditions when present in the gut, and include dozens of biofilm- and antimicrobial resistance-related genes. This work provides an overview of the microbial communities populating the stents., (© 2024. The Author(s).)

We performed a longitudinal shotgun metagenomic investigation of the plaque microbiome associated with peri-implant diseases in a cohort of 91 subjects with 320 quality-controlled metagenomes. Through recently improved taxonomic profiling methods, we identified the most discriminative species between healthy and diseased subjects at baseline, evaluated their change over time, and provided evidence that clinical treatment had a positive effect on plaque microbiome composition in patients affected by mucositis and peri-implantitis., (© 2024. The Author(s).)

The oral microbiota plays an important role in the exogenous nitrate reduction pathway and is associated with heart and periodontal disease and cigarette smoking. We describe smoking-related changes in oral microbiota composition and resulting potential metabolic pathway changes that may explain smoking-related changes in disease risk. We analyzed health information and salivary microbiota composition among 1601 Cooperative Health Research in South Tyrol participants collected 2017-2018. Salivary microbiota taxa were assigned from amplicon sequences of the 16S-V4 rRNA and used to describe microbiota composition and predict metabolic pathways. Aerobic taxa relative abundance decreased with daily smoking intensity and increased with years since cessation, as did inferred nitrate reduction. Former smokers tended to be more similar to Never smokers than to Current smokers, especially those who had quit for longer than 5 years. Cigarette smoking has a consistent, generalizable association on oral microbiota composition and predicted metabolic pathways, some of which associate in a dose-dependent fashion. Smokers who quit for longer than 5 years tend to have salivary microbiota profiles comparable to never smokers., (© 2023. The Author(s).)

Whilst most individuals with SARS-CoV-2 infection have relatively mild disease, managed in the community, it was noted early in the pandemic that individuals with cardiovascular risk factors were more likely to experience severe acute disease, requiring hospitalisation. As the pandemic has progressed, increasing concern has also developed over long symptom duration in many individuals after SARS-CoV-2 infection, including among the majority who are managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined. Here, we examine post-illness metabolomic profiles, using nuclear magnetic resonance (Nightingale Health Oyj), and gut-microbiome profiles, using shotgun metagenomic sequencing (Illumina Inc), in 2561 community-dwelling participants with SARS-CoV-2. Illness duration ranged from asymptomatic (n = 307) to Post-COVID Syndrome (n = 180), and included participants with prolonged non-COVID-19 illnesses (n = 287). We also assess a pre-established metabolomic biomarker score, previously associated with hospitalisation for both acute pneumonia and severe acute COVID-19 illness, for its association with illness duration. We found an atherogenic-dyslipidaemic metabolic profile, including biomarkers such as fatty acids and cholesterol, was associated with longer duration of illness, both in individuals with and without SARS-CoV-2 infection. Greater values of a pre-existing metabolomic biomarker score also associated with longer duration of illness, regardless of SARS-CoV-2 infection. We found no association between illness duration and gut microbiome profiles in convalescence. This highlights the potential role of cardiometabolic dysfunction in relation to the experience of long duration symptoms after symptoms of acute infection, both COVID-19 as well as other illnesses., (© 2023. The Author(s).)

The human microbiome is an integral component of the human body and a co-determinant of several health conditions 1,2 . However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown 3,4 . Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies 5 , especially those on non-infectious, microbiome-associated diseases., (© 2023. The Author(s).)

Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts., (© 2023. Springer Nature Limited.)

Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (n = 102) spanning 3 to 5 generations over the same female bloodline. We observe microbiome community composition associated with kinship, with seven low abundant genera displaying familial distribution patterns. While kinship and current cohabitation emerge as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter's age and being higher among cohabiting pairs than those living apart. Although rare, we detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation., (© 2021. The Author(s).)

The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation., (© 2021. The Author(s).)

A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFNγ-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.

Loss of gut microbial diversity 1-6 in industrial populations is associated with chronic diseases 7 , underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.

Dental implants are installed in an increasing number of patients. Mucositis and peri-implantitis are common microbial-biofilm-associated diseases affecting the tissues that surround the dental implant and are a major medical and socioeconomic burden. By metagenomic sequencing of the plaque microbiome in different peri-implant health and disease conditions (113 samples from 72 individuals), we found microbial signatures for peri-implantitis and mucositis and defined the peri-implantitis-related complex (PiRC) composed by the 7 most discriminative bacteria. The peri-implantitis microbiome is site specific as contralateral healthy sites resembled more the microbiome of healthy implants, while mucositis was specifically enriched for Fusobacterium nucleatum acting as a keystone colonizer. Microbiome-based machine learning showed high diagnostic and prognostic power for peri-implant diseases and strain-level profiling identified a previously uncharacterized subspecies of F. nucleatum to be particularly associated with disease. Altogether, we associated the plaque microbiome with peri-implant diseases and identified microbial signatures of disease severity.

The microbiota has been shown to promote intestinal tumourigenesis, but a possible anti-tumourigenic effect has also been postulated. Here, we demonstrate that changes in the microbiota and mucus composition are concomitant with tumourigenesis. We identified two anti-tumourigenic strains of the microbiota-Faecalibaculum rodentium and its human homologue, Holdemanella biformis-that are strongly under-represented during tumourigenesis. Reconstitution of Apc Min/+ or azoxymethane- and dextran sulfate sodium-treated mice with an isolate of F. rodentium (F. PB1) or its metabolic products reduced tumour growth. Both F. PB1 and H. biformis produced short-chain fatty acids that contributed to control protein acetylation and tumour cell proliferation by inhibiting calcineurin and NFATc3 activation in mouse and human settings. We have thus identified endogenous anti-tumourigenic bacterial strains with strong diagnostic, therapeutic and translational potential.

The dysbiosis of the oral microbiome is associated with both localized and systemic diseases. Modulating the resident microbial communities by the dietary consumption of probiotics has become an appealing means to promote host health by either restoring host-microbe balance or preventing dysbiosis. Most probiotics strategies target the intestinal microbiome, but little is known about their impact on the oral microbiome. We analyzed here the saliva microbiome from 21 volunteers, longitudinally collected before, during, and after consumption of a commercial probiotic and a standard yoghurt using 16S amplicon sequencing. The alpha diversity of the saliva microbiome had a statistically significant increase (P-value = 0.0011) in one of the groups that consumed the probiotic. The overall structure of the microbiome was however not significantly impacted by the probiotic, although oligotyping analysis revealed that both Streptococci and Lactobacilli present in the probiotic product persisted in the saliva microbiome. In contrast, non-probiotic yoghurt consumption had a lesser impact on the overall diversity and Lactobacillus and Streptococcus persistence. Our results suggest that consumption of commercial probiotics in healthy subjects increase the overall diversity of the oral cavity microbiome in the short term, but such dietary interventions are not able to substantially modify the structure of the microbiome.

Psoriasis is an immune-mediated inflammatory skin disease that has been associated with cutaneous microbial dysbiosis by culture-dependent investigations and rRNA community profiling. We applied, for the first time, high-resolution shotgun metagenomics to characterise the microbiome of psoriatic and unaffected skin from 28 individuals. We demonstrate psoriatic ear sites have a decreased diversity and psoriasis is associated with an increase in Staphylococcus , but overall the microbiomes of psoriatic and unaffected sites display few discriminative features at the species level. Finer strain-level analysis reveals strain heterogeneity colonisation and functional variability providing the intriguing hypothesis of psoriatic niche-specific strain adaptation or selection. Furthermore, we accessed the poorly characterised, but abundant, clades with limited sequence information in public databases, including uncharacterised Malassezia spp. These results highlight the skins hidden diversity and suggests strain-level variations could be key determinants of the psoriatic microbiome. This illustrates the need for high-resolution analyses, particularly when identifying therapeutic targets. This work provides a baseline for microbiome studies in relation to the pathogenesis of psoriasis.

Mycobacterium tuberculosis and Mycobacterium leprae have remained, for many years, the primary species of the genus Mycobacterium of clinical and microbiological interest. The other members of the genus, referred to as nontuberculous mycobacteria (NTM), have long been underinvestigated. In the last decades, however, the number of reports linking various NTM species with human diseases has steadily increased and treatment difficulties have emerged. Despite the availability of whole genome sequencing technologies, limited effort has been devoted to the genetic characterization of NTM species. As a consequence, the taxonomic and phylogenetic structure of the genus remains unsettled and genomic information is lacking to support the identification of these organisms in a clinical setting. In this work, we widen the knowledge of NTMs by reconstructing and analyzing the genomes of 41 previously uncharacterized NTM species. We provide the first comprehensive characterization of the genomic diversity of NTMs and open new venues for the clinical identification of opportunistic pathogens from this genus.

Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments.

Microbes play key roles in shaping the physiology of insects and can influence behavior, reproduction and susceptibility to pathogens. In Sub-Saharan Africa, two major malaria vectors, Anopheles gambiae and An. coluzzii, breed in distinct larval habitats characterized by different microorganisms that might affect their adult physiology and possibly Plasmodium transmission. We analyzed the reproductive microbiomes of male and female An. gambiae and An. coluzzii couples collected from natural mating swarms in Burkina Faso. 16S rRNA sequencing on dissected tissues revealed that the reproductive tracts harbor a complex microbiome characterized by a large core group of bacteria shared by both species and all reproductive tissues. Interestingly, we detected a significant enrichment of several gender-associated microbial biomarkers in specific tissues, and surprisingly, similar classes of bacteria in males captured from one mating swarm, suggesting that these males originated from the same larval breeding site. Finally, we identified several endosymbiotic bacteria, including Spiroplasma, which have the ability to manipulate insect reproductive success. Our study provides a comprehensive analysis of the reproductive microbiome of important human disease vectors, and identifies a panel of core and endosymbiotic bacteria that can be potentially exploited to interfere with the transmission of malaria parasites by the Anopheles mosquito.

Bifidobacteria are common and frequently dominant members of the gut microbiota of many animals, including mammals and insects. Carbohydrates are considered key carbon sources for the gut microbiota, imposing strong selective pressure on the complex microbial consortium of the gut. Despite its importance, the genetic traits that facilitate carbohydrate utilization by gut microbiota members are still poorly characterized. Here, genome analyses of 47 representative Bifidobacterium (sub)species revealed the genes predicted to be required for the degradation and internalization of a wide range of carbohydrates, outnumbering those found in many other gut microbiota members. The glycan-degrading abilities of bifidobacteria are believed to reflect available carbon sources in the mammalian gut. Furthermore, transcriptome profiling of bifidobacterial genomes supported the involvement of various chromosomal loci in glycan metabolism. The widespread occurrence of bifidobacterial saccharolytic features is in line with metagenomic and metatranscriptomic datasets obtained from human adult/infant faecal samples, thereby supporting the notion that bifidobacteria expand the human glycobiome. This study also underscores the hypothesis of saccharidic resource sharing among bifidobacteria through species-specific metabolic specialization and cross feeding, thereby forging trophic relationships between members of the gut microbiota.