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Maurice, C. F.

Publications and source records attributed to Maurice, C. F..

17 recordsLinked to original sources

Discovery of a hydrolysis operon in Lachnospiraceae provides a genetic basis to understanding castalagin metabolism by the human microbiome in a clinical study.

Gut microbes metabolize the ellagitannin castalagin to ellagic acid and urolithins, a process associated with health effects for the host. Despite the use of the castalagin-rich camu camu extracts in clinical trials, the genes and taxa responsible for castalagin hydrolysis remain elusive. We used multi-omics to discover a castalagin associated hydrolase (cah) operon sparsely distributed in Lachnospiraceae. Analysis of fecal samples from a camu camu supplementation clinical trial demonstrates functional redundancy with prevalence of cah and other ellagic acid metabolism genes in different taxa explaining the prevalence of metabolites. Employing genome mining strategies, we discovered and validated ellagitannin metabolism genes in uncharacterized and uncultured species. We further identified flavogallonic acid as a prevalent metabolite of castalagin in human fecal samples. Collectively, this work provides a genetic basis for castalagin metabolism to urolithins and flavogallonic acid end-metabolites and sets the stage to study the role of metabolism in clinical trials.

microbiology↗

The Microbiota Dictates Vendor-Derived Differences in a Murine Clostridioides difficile Infection Model

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea and remains a major burden to healthcare systems worldwide. The development of novel therapeutics for CDI requires robust and reproducible preclinical models. However, the microbiota has emerged as a major source of variability in animal studies. Here, we found that genetically similar mice obtained from two commercial vendors, Jackson Laboratory (JAX) and Charles River Laboratories (CRL), exhibited marked differences in susceptibility to CDI, with JAX mice developing fulminant disease and CRL mice remaining resistant. Using full-length 16S rRNA gene sequencing, we show that JAX and CRL mice harboured distinct gut microbiota, and that cohousing susceptible JAX mice with resistant CRL mice was sufficient to shift the JAX microbiota toward the CRL community structure and confer resistance to CDI. Differential abundance analysis identified taxa distinguishing resistant and susceptible mice, providing candidates for future mechanistic investigation. These findings demonstrate that vendor-derived variation in the gut microbiota drives differential susceptibility to CDI in mice, and that this phenotype is transferable via cohousing, highlighting the importance of accounting for the microbiota when designing and interpreting animal models of infectious disease.

microbiology↗

A human microbiota-associated mouse model of early-life malnutrition reveals persistent microbiome immaturity and limited response to fecal viral transplantation

Malnutrition is a leading cause of child mortality worldwide and has long-lasting health and socio-economic consequences. Studies have established causal links between the gut microbiota and childhood malnutrition, with key microbial signatures including delayed microbiome development and an enrichment of bacterial pathogens. While current dietary interventions improve growth and developmental outcomes, post-therapy regression to an immature microbial state is common. Fecal virome transplants (FVTs) represent a promising approach to reshape gut microbial communities, yet their therapeutic potential in early life remains poorly described. In this work, we established a diet-inducible human microbiota-associated (HMA) mouse model of early-life stunting, where malnourished pups were 35% lighter and 25% shorter than healthy controls. We developed a predictive model to quantify gut bacteriome development, identifying Enterococcus and Clostridium as primary drivers of healthy maturation. Our model revealed that the malnourished HMA mouse gut remains significantly immature compared to healthy controls and decoupled from the mouse's chronological age. While a successful FVT from a healthy donor induced targeted changes in specific bacterial taxa, including a significant increase in Enterococcus species, it did not rescue physical growth or lead to broad community-level shifts. In contrast, a failed FVT from a different healthy donor revealed a significant mismatch between the donor virome and recipient bacteriome, indicating niche incompatibility that limits FVT efficacy. Our work establishes a robust human microbiota-associated mouse model for studying maturation of the gut in early life, suggesting that FVT alone is insufficient to reproducibly reshape the malnourished gut. These findings highlight the need for synergistic strategies, combining viral interventions with nutritional supplementation for maximum therapeutic effect.

microbiology↗

Temperate phage microdiversity reflects infant gut microbiome maturation independent of chronic undernutrition

The assembly and maturation of the infant gut microbiome is a critical developmental process. Yet the dynamics of the viral community, particularly in the context of stunting (chronic malnutrition) remain underexplored. Leveraging longitudinal fecal metagenomes from Zimbabwean infants with normal and stunted growth trajectories, we characterized the development of the gut bacterial and temperate phage communities from birth to 18 moths old. We found that infant gut temperate phages target hallmark early-life bacterial taxa, such as Bifidobacteriaceae, and exhibit an age-dependent maturation that parallels bacterial succession. Notably, both bacterial and temperate phage alpha diversity increased with age. This contrasts with previous studies focused on the extracellular viral fraction and highlights a strong coupling between prophage early-life dynamics and during bacterial gut colonization. Using abundance-based maturation models, we identified successional phases of colonization for both bacteria and their associated temperate viral clusters. Importantly, a viral microdiversity maturation model provided a stronger prediction of chronological age than viral abundance-based model, revealing within-phage genomic variation as a key signal of virome assembly, particularly around weaning. Contrary to findings in wasting (or severe acute malnutrition), stunted growth trajectories were not associated with a significant delay in either bacterial or temperate phage maturation. These results demonstrate that viral genomic variation is a new, informative dimension of early-life gut microbial assembly and that stunting may not impair infants gut maturation process. ImportanceThe early-life period represents a critical window for the establishment of the gut microbial communities, a process that is often affected by environmental factors such as diet. While severe acute malnutrition (SAM) is known to delay bacterial maturation, the impact of chronic, moderate undernutrition, such as stunting is poorly understood. Stunting is a highly prevalent global health condition with irreversible consequences on long-term host health, yet its implications on gut microbiome assembly remain unclear. Our study provides novel insights into the maturation of temperate phages, which to prime the infant gut by colonizing alongside their bacterial hosts and acting as drivers of bacterial evolution via lysogeny. By demonstrating that viral strain-level (genomic) variation captures a stronger age-related signal than viral abundance, we identified an underexplored dimension of microbial assembly. The finding that stunting, in contrast to SAM, does not impact microbial maturation provides essential context for public health interventions and future studies addressing this condition.

bioinformatics↗

The infant gut virome assembles rapidly and predictably over the first three years of life

Assembly of the gut microbiota in infancy is an important health determinant, yet the viral component, the virome, remains poorly described. Here, we conduct a meta-analysis of 12 infant cohorts across 8 countries to model gut virome development over the first three years of life. Our results revealed distinct diversity patterns, where viral richness increased significantly over the first eight months of life alongside a loss of community evenness. We define virome developmental velocity, the rate of change between sequential samples, which significantly decreased over time. This was mirrored by community-wide convergence, as infant viromes became more similar with age. Functionally, the transition to a stable state involved a significant decrease in extracellular temperate phages and shifts in phage-encoded auxiliary metabolic genes, which can modulate host metabolism. Our work provides a baseline characterization of gut virome development, marked by a conserved successional trajectory, providing a framework to identify disease-associated perturbations.

bioinformatics↗

Strain-level and phenotypic stability contrasts with plasmid and phage variability in water kefir communities

Microbial communities can change in response to top-down factors, such as phages, and bottom-up factors, such as nutrient availability. Previous studies have successfully investigated bacterial species-level dynamics, but diversity and interactions beyond the species-level is usually lacking. Traditional fermented foods, such as water kefir, provide ideal systems to study ecological and evolutionary dynamics beyond the species-level, as they are simple and trackable systems that are cultivated in non-sterile, nutrient-rich environments which foster microbial growth and invasion. Despite the central role of only a few lactic acid bacteria for fermentation, little is known about the genomic diversity and dynamics of these community members over time. Within the framework of a graduate course, 35 students propagated water kefir across several generations under different nutrient conditions and in different households to study microbial responses over time. We found that water kefir communities were generally stable at the species-level, with only rare bacterial species replaced over long timescales (more than 2 years). While we observed little strain-level diversity with few strain replacements over long timescales, closely related strains exhibited variation in accessory gene content, often encoded on plasmids, particularly those involved in ecologically meaningful functions such as sugar utilization pathways and phage defense systems. We hypothesise that these genomic variations could reflect the adaptations of strains to different sugars and phages. Consistent with this, we observed a diverse array of phages, many likely originating from the unique household environments. By documenting the genomic landscape of microbial species, strains, plasmids, and phages, this study advances our understanding of the diversity and dynamics of microbial communities in fermented foods. Furthermore, our course material is publicly available and offers a blueprint for bridging the gap between teaching and research, inspiring the next generation of scientists to unravel the complexities of microbial ecosystems. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/640646v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@56db6borg.highwire.dtl.DTLVardef@5f6dc6org.highwire.dtl.DTLVardef@11fff14org.highwire.dtl.DTLVardef@1a37a9f_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Prophage induction contributes to alterations in the gut phageome during intestinal inflammation

Bacteriophages (phages) are abundant members of the gut microbiota and regulators of bacterial communities. During homeostasis, gut phage communities are longitudinally stable and lysogenic replication is dominant. In chronic gut inflammatory disorders, such as inflammatory bowel diseases (IBDs), there are alterations in phage diversity, which may result from changes in phage replication cycle dynamics. Here, we used a combination of in vitro, simplified community, and whole-community bioinformatics approaches to investigate whether prophage induction contributes to these alterations. We identified several compounds associated with gut inflammation that induced prophages in commensal gut bacterial isolates. Analysing data from two mouse models of colitis, we observed that shifts in the composition of temperate phages occur over the course of inflammation, supporting a switch from lysogenic to lytic replication. Collectively, our observations support the idea that prophage induction contributes to alterations in the phageome associated with inflammation.

microbiology↗

Improving gut virome comparisons using predicted phage host information

The human gut virome is predominantly made up of bacteriophages (phages), viruses that infect bacteria. Metagenomic studies have revealed that phages in the gut are highly individual specific and dynamic. These features make it challenging to perform meaningful cross-study comparisons. While several taxonomy frameworks exist to group phages and improve these comparisons, these strategies provide little insight into the potential effects phages have on their bacterial hosts. Here, we propose the use of predicted phage host families (PHFs) as a functionally relevant, higher rank unit of phage taxonomy to improve these cross-study analyses. We first show that bioinformatic predictions of phage hosts are accurate at the host family level by measuring their concordance to Hi-C sequencing-based predictions in human and mouse fecal samples. Next, using phage host family predictions, we determined that PHFs reduce intra- and interindividual ecological distances compared to viral contigs in a previously published cohort of 10 healthy individuals, while simultaneously improving longitudinal virome stability. Lastly, by reanalyzing a previously published metagenomics dataset with > 1,000 samples, we determined that PHFs are prevalent across individuals and can aid in the detection of inflammatory bowel disease-specific virome signatures. Overall, our analyses support the use of predicted phage hosts in reducing between-sample distances and providing a biologically relevant framework for making between-sample virome comparisons.

bioinformatics↗

Identification of novel fructo-oligosaccharide bacterial consumers by pulse metatranscriptomics in a human stool sample

Dietary fibres influence the composition of the human gut microbiota and directly contribute to its downstream effects on host health. As more research supports the use of glycans as prebiotics for therapeutic applications, the need to identify the gut bacteria that metabolize glycans of interest increases. Fructooligosaccharide (FOS) is a common diet-derived glycan that is fermented by the gut microbiota and has been used as a prebiotic. Despite being well studied, we do not yet have a complete picture of all FOS-consuming gut bacterial taxa. To identify new bacterial consumers, we used a short exposure of microbial communities in a stool sample to FOS or galactomannan as the sole carbon source to induce glycan metabolism genes. We then performed metatranscriptomics, paired with whole metagenomic sequencing (WMS), and 16S amplicon sequencing. The short incubation induced genes involved in carbohydrate metabolism, like carbohydrate-active enzymes (CAZymes), including glycoside hydrolase family 32 genes, which hydrolyze fructan polysaccharides like FOS and inulin. Interestingly, FOS metabolism transcripts were notably overexpressed in Blautia species not previously reported to be fructan consumers. We therefore validated the ability of different Blautia species to ferment fructans by monitoring their growth and fermentation in defined media. This pulse metatranscriptomics approach is a useful method to find novel consumers of prebiotics and increase our understanding of prebiotic metabolism by CAZymes in the gut microbiota. SignificanceComplex carbohydrates are key contributors to the composition of the human gut microbiota and play an essential role in the microbiotas effects on host health. Understanding which bacteria consume complex carbohydrates, or glycans, provides a mechanistic link between dietary prebiotics and their beneficial health effects, an essential step for their therapeutic application. Here, we used a pulse metatranscriptomics pipeline to identify bacterial consumers based on glycan metabolism induction in a human stool sample. We identified novel consumers of FOS among Blautia species, expanding our understanding of this well-known glycan. Our approach can be applied to identify consumers of understudied glycans and expand our prebiotic repertoire. It can also be used to study prebiotic glycans directly in stool samples in distinct patient populations to help delineate the prebiotic mechanism.

microbiology↗

Optimization of an improved, time-saving, and scalable, protocol for the extraction of DNA from diverse viromes

IntroductionThe virome, composed of viruses inhabiting diverse ecosystems, significantly influences microbial community dynamics and host health. The phenol-chloroform DNA extraction protocol for viromes, though effective, is time-intensive and requires the use of multiple toxic chemicals. MethodsThis study introduces a streamlined, scalable protocol for DNA extraction using a commercially-available kit as an alternative, assessing its performance against the phenol-chloroform method across human fecal, mouse fecal, and soil samples. ResultsNo significant differences in virome diversity or community composition were seen between methods. Most viral operational taxonomic units (vOTUs) were common to both methods, with only a small percentage unique to either approach. Alpha- and beta-diversity analyses showed no significant impact of the extraction method on virome composition, confirming the kits efficacy and versatility. ConclusionsWhile the kit approach offers benefits like reduced toxicity and increased throughput, it has limitations such as higher costs and potential issues reliably capturing low-abundance taxa. This protocol provides a viable option for large-scale virome studies, although the phenol-chloroform approach may still be preferable for specific sample types.

microbiology↗

Prevalent human gut Enterocloster spp. produce urolithin A from its dietary precursor using a molybdenum-dependent dehydroxylase

Urolithin A (uroA) is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota that can affect host health by stimulating mitophagy. Most individuals harbor a microbiota capable of uroA production; however, the mechanisms underlying the dehydroxylation of its catechol-containing dietary precursor (uroC) are unknown. Here, we use a combination of untargeted bacterial transcriptomics, proteomics, and comparative genomics to uncover an inducible uroC dehydroxylase (ucd) operon in Enterocloster spp. We show that Enterocloster spp. are sensitive to iron chelation by uroC, and dehydroxylation to uroA rescues growth by disrupting the iron-binding catechol. Importantly, only microbiota samples actively transcribing ucd could produce uroA, establishing ucd-containing Enterocloster spp. as keystone urolithin metabolizers. Overall, this work identifies Enterocloster spp. and the ucd operon as main contributors to uroA production and establishes a multi-omics framework to further our mechanistic understanding of polyphenol metabolism by the human gut microbiota.

microbiology↗

Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria

The bacteria living in the human gut are essential for host health. Though the composition and metabolism of these bacteria is well described in both healthy hosts and those with intestinal disease, less is known about the activity of the gut bacteria prior to, and during, disease development - especially regarding gut bacterial replication. Here, we use a recently developed single-cell technique alongside existing metagenomics-based tools to identify, track, and quantify the replicating gut bacteria and their replication dynamics in the dextran sodium sulfate mouse model of colitis. We show that the proportion of replicating gut bacteria decreases when mice have the highest levels of inflammation and returns to baseline levels as mice begin recovering. We additionally report significant alterations in the composition of the total replicating gut bacterial community during colitis development. On the taxa level, we observe significant changes in the abundance of taxa such as the mucus-degrading Akkermansia muciniphila and the poorly described Erysipelatoclostridium genus. We further demonstrate that many taxa exhibit variable replication rates during colitis, including A. muciniphila. Lastly, we show that colitis development is positively correlated with increases in the presence and abundance of bacteria predicted to be fast replicators, suggesting that taxa with the potential to replicate quickly may have an advantage during intestinal inflammation. These data support the need for additional research using activity-based approaches to further characterize the gut bacterial response to intestinal inflammation and its consequences for both the host and the gut microbial community at large. ImportanceIt is well known that the bacteria living inside the gut are important for human health. Indeed, the type of bacteria which are present and their metabolism is different in healthy people versus those with intestinal disease. However, less is known about how these gut bacteria are replicating, especially as someone begins to develop intestinal disease. This is especially important as it is thought that the active gut bacteria may be more relevant to health. Here, we begin addressing this gap by using several complementary approaches to characterize the replicating gut bacteria in a mouse model of intestinal inflammation. We reveal which gut bacteria are replicating, and how quickly, as mice develop and recover from inflammation. This work can serve as a model for future research to identify how the active gut bacteria may be impacting health, or why these particular bacteria tend to thrive during intestinal inflammation.

microbiology↗

Actively replicating gut bacteria identified by 5-ethyhyl-2'-deoxyuridine (EdU) click chemistry and cell sorting

The composition of the intestinal bacterial community is well described, but recent research suggests that the metabolism of these bacteria plays a larger role in health than which species are present. One fundamental aspect of gut bacterial metabolism that remains understudied is bacterial replication. Indeed, there exist few techniques which can identify actively replicating gut bacteria. In this study, we aimed to address this gap by adapting 5-ethynyl-2-deoxyuridine (EdU) click chemistry (EdU-click), a metabolic labeling method, coupled with fluorescence-activated cell sorting and sequencing (FACS-Seq) to characterize replicating gut bacteria. We first used EdU-click with human gut bacterial isolates and show that many of them are amenable to this technique. We then optimized EdU-click and FACS-Seq for murine fecal bacteria and reveal that Prevotella UCG-001 and Ileibacterium are enriched in the replicating fraction. Finally, we labelled the actively replicating murine gut bacteria during exposure to cell wall-specific antibiotics in vitro. We show that regardless of the antibiotic used, the actively replicating bacteria largely consist of Ileibacterium, suggesting the resistance of this taxon to perturbations. Overall, we demonstrate how combining EdU-click and FACSeq can identify the actively replicating gut bacteria and their link with the composition of the whole community in both homeostatic and perturbed conditions. This technique will be instrumental in elucidating in situ bacterial replication dynamics in a variety of other ecological states, including colonization and species invasion, as well as for investigating the relationship between the replication and abundance of bacteria in complex communities.

microbiology↗

Bacteriophages Playing Nice: Lysogenic bacteriophage replication stable in the human gut microbiota

1.1.The human gut is a dense microbial community, of which bacteria and bacteriophages are the majority. Bacteriophages, viruses of bacteria, exist stably, without major fluctuations in the gut of healthy individuals. This stability appears to be due to an absence of kill-the-winner dynamics, and the existence of piggy-back-the-winner dynamics, where lysogenic replication rather than lytic replication occurs. Revisiting the deep-viral sequencing data of a healthy individual studied over 2.4 years, we were able to improve our understanding of how these dynamics occur in healthy individuals. We assembled prophages from bacterial metagenomic data and show that these prophages were continually switching from lysogenic to lytic replication. Prophages were the source of a stable extracellular phage population continually present in low abundance, in comparison to the lytic-phage population, where taxonomic diversity diverged over 2.4 years. The switch to lytic replication, or prophage induction, appears to occur mostly through spontaneous prophage induction. The observed phage dynamics of regular spontaneous induction are ecologically important as they allow prophages to maintain their ability to replicate, avoiding degradation and their loss from the gut microbiota. 1.2. Significance StatementIt has been eight years since Minot and colleagues published their landmark longitudinal study of phages in the gut. In the years following, the bioinformatic field improved in great strides, including the methods of bacterial-genome assembly, phage-identification, and prophage detection. We leveraged the unprecedented deep sequencing of phages in this dataset by adding bacterial assembly and prophage detection analyzes. We show clearly for the first time that piggy-back-the-winner dynamics are maintained in the gut through spontaneous prophage induction, and not widespread triggered prophage induction. These dynamics play an important ecological role by creating a stable subpopulation of phages, which could help explain how phages are maintained over the 2.4 years timeframe that this individual was studied.

microbiology↗

OnePetri: accelerating common bacteriophage Petri dish assays with computer vision

IntroductionBacteriophage plaque enumeration is a critical step in a wide array of protocols. The current gold standard for plaque enumeration on Petri dishes is through manual counting. This approach is time-intensive, has low-throughput, is limited to Petri dishes which have a countable number of plaques, and can have variable results upon recount due to human error. MethodsWe present OnePetri, a collection of trained machine learning models and open-source mobile application for the rapid enumeration of bacteriophage plaques on circular Petri dishes. ResultsWhen compared against the current gold standard of manual counting, OnePetri was significantly faster, with minimal error. Compared against two other similar tools, Plaque Size Tool and CFU.AI, OnePetri had higher plaque recall and reduced detection times on most test images. ConclusionsThe OnePetri application can rapidly enumerate phage plaques on circular Petri dishes with high precision and recall.

bioinformatics↗

Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates severity of DSS-colitis

Inflammatory bowel diseases (IBDs) including Crohns disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages) is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown. Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs. Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease.

microbiology↗

Translational activity is uncoupled from nucleic acid content in bacterial cells of the human gut microbiota

BackgroundChanges in bacterial diversity in the human gut microbiome, characterized primarily though DNA sequencing methods, have been associated with many different adverse health conditions. However, these changes do not always reflect changes in bacterial activity, and thus how the gut microbiome is implicated in disease is still not often understood. New methods that link together bacterial function to bacterial identity are needed to further explore the role of the gut microbiome in health and disease. We optimized bioorthogonal non-canonical amino acid tagging (BONCAT) for the gut microbiota and combined it with fluorescently activated cell sorting and sequencing (FACS-Seq) to identify the translationally active members of the community. We then used this novel technique to compare and contrast to other methods of bulk community measurements of activity and viability: physiological staining of relative nucleic acid content and membrane damage. Relative nucleic acid content has previously been linked to metabolic activity, yet remains currently undefined for the human gut microbiota. ResultsTen healthy, unrelated individuals were sampled to determine the proportion and diversity of distinct physiological fractions of their gut microbiota. The translationally active bacteria represent about half of the gut microbiota, and are not distinct from the whole community. The high nucleic acid content (HNA) bacteria also represent about half of the gut microbiota, but are distinct from the whole community and correlate with the damaged subset. Perturbing the community with xenobiotics previously shown to alter bacterial activity but not diversity resulted in stronger changes in the distinct physiological fractions than in the whole community. ConclusionsBONCAT is a suitable method to probe the translationally active members of the human gut microbiota, and combined with FACS-Seq, allows for their identification. The high nucleic acid content bacteria are not necessarily the protein-producing bacteria in the community, and so further work is needed to understand the relationship between nucleic acid content and bacterial metabolism in the human gut. Taking into account physiologically distinct subsets of the gut microbiota may be more informative than relying on whole community profiling.

microbiology↗