Publications by authors named "Curtis Huttenhower"

236 Publications

A statistical model for describing and simulating microbial community profiles.

PLoS Comput Biol 2021 Sep 13;17(9):e1008913. Epub 2021 Sep 13.

Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Many methods have been developed for statistical analysis of microbial community profiles, but due to the complex nature of typical microbiome measurements (e.g. sparsity, zero-inflation, non-independence, and compositionality) and of the associated underlying biology, it is difficult to compare or evaluate such methods within a single systematic framework. To address this challenge, we developed SparseDOSSA (Sparse Data Observations for the Simulation of Synthetic Abundances): a statistical model of microbial ecological population structure, which can be used to parameterize real-world microbial community profiles and to simulate new, realistic profiles of known structure for methods evaluation. Specifically, SparseDOSSA's model captures marginal microbial feature abundances as a zero-inflated log-normal distribution, with additional model components for absolute cell counts and the sequence read generation process, microbe-microbe, and microbe-environment interactions. Together, these allow fully known covariance structure between synthetic features (i.e. "taxa") or between features and "phenotypes" to be simulated for method benchmarking. Here, we demonstrate SparseDOSSA's performance for 1) accurately modeling human-associated microbial population profiles; 2) generating synthetic communities with controlled population and ecological structures; 3) spiking-in true positive synthetic associations to benchmark analysis methods; and 4) recapitulating an end-to-end mouse microbiome feeding experiment. Together, these represent the most common analysis types in assessment of real microbial community environmental and epidemiological statistics, thus demonstrating SparseDOSSA's utility as a general-purpose aid for modeling communities and evaluating quantitative methods. An open-source implementation is available at http://huttenhower.sph.harvard.edu/sparsedossa2.
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http://dx.doi.org/10.1371/journal.pcbi.1008913DOI Listing
September 2021

Metatranscriptomics for the Human Microbiome and Microbial Community Functional Profiling.

Annu Rev Biomed Data Sci 2021 07 13;4:279-311. Epub 2021 May 13.

Harvard Chan Microbiome in Public Health Center and Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA; email:

Shotgun metatranscriptomics (MTX) is an increasingly practical way to survey microbial community gene function and regulation at scale. This review begins by summarizing the motivations for community transcriptomics and the history of the field. We then explore the principles, best practices, and challenges of contemporary MTX workflows: beginning with laboratory methods for isolation and sequencing of community RNA, followed by informatics methods for quantifying RNA features, and finally statistical methods for detecting differential expression in a community context. In thesecond half of the review, we survey important biological findings from the MTX literature, drawing examples from the human microbiome, other (nonhuman) host-associated microbiomes, and the environment. Across these examples, MTX methods prove invaluable for probing microbe-microbe and host-microbe interactions, the dynamics of energy harvest and chemical cycling, and responses to environmental stresses. We conclude with a review of open challenges in the MTX field, including making assays and analyses more robust, accessible, and adaptable to new technologies; deciphering roles for millions of uncharacterized microbial transcripts; and solving applied problems such as biomarker discovery and development of microbial therapeutics.
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http://dx.doi.org/10.1146/annurev-biodatasci-031121-103035DOI Listing
July 2021

A bacterial bile acid metabolite modulates T activity through the nuclear hormone receptor NR4A1.

Cell Host Microbe 2021 09 19;29(9):1366-1377.e9. Epub 2021 Aug 19.

Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address:

Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4 T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (T cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on T cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.
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http://dx.doi.org/10.1016/j.chom.2021.07.013DOI Listing
September 2021

The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men.

Clin Transl Gastroenterol 2021 Aug 1;12(8):e00338. Epub 2021 Aug 1.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

Methods: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

Results: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% of whom had available tissue data. After accounting for multiple hypothesis testing, the relationship between the sulfur microbial diet and CRC incidence did not differ by subtype. However, there was a suggestion of an association by prostaglandin synthase 2 (PTGS2) status with a multivariable adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.31 (95% confidence interval: 0.99-1.74, Ptrend = 0.07, Pheterogeneity = 0.04) for PTGS2-high CRC. The association of the sulfur microbial diet with distal CRC seemed to differ by the presence of intratumoral Bifidobacterium spp. with an adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.65 (95% confidence interval: 1.14-2.39, Ptrend = 0.01, Pheterogeneity = 0.03) for Bifidobacterium-negative distal CRC. We observed no apparent heterogeneity by other tested molecular markers.

Discussion: Greater long-term adherence to the sulfur microbial diet could be associated with PTGS2-high and Bifidobacterium-negative distal CRC in men. Additional studies are needed to further characterize the role of gut microbial sulfur metabolism and CRC.
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http://dx.doi.org/10.14309/ctg.0000000000000338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323793PMC
August 2021

The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.

Gastroenterology 2021 Jul 14. Epub 2021 Jul 14.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Electronic address:

Background & Aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (HS), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking.

Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (OR, 1.31; 95% CI, 1.10-1.56, P = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (OR, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; P = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50.

Conclusions: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.
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http://dx.doi.org/10.1053/j.gastro.2021.07.008DOI Listing
July 2021

Statistical approaches for differential expression analysis in metatranscriptomics.

Bioinformatics 2021 07;37(Suppl_1):i34-i41

Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.

Motivation: Metatranscriptomics (MTX) has become an increasingly practical way to profile the functional activity of microbial communities in situ. However, MTX remains underutilized due to experimental and computational limitations. The latter are complicated by non-independent changes in both RNA transcript levels and their underlying genomic DNA copies (as microbes simultaneously change their overall abundance in the population and regulate individual transcripts), genetic plasticity (as whole loci are frequently gained and lost in microbial lineages) and measurement compositionality and zero-inflation. Here, we present a systematic evaluation of and recommendations for differential expression (DE) analysis in MTX.

Results: We designed and assessed six statistical models for DE discovery in MTX that incorporate different combinations of DNA and RNA normalization and assumptions about the underlying changes of gene copies or species abundance within communities. We evaluated these models on multiple simulated and real multi-omic datasets. Models adjusting transcripts relative to their encoding gene copies as a covariate were significantly more accurate in identifying DE from MTX in both simulated and real datasets. Moreover, we show that when paired DNA measurements (metagenomic data) are not available, models normalizing MTX measurements within-species while also adjusting for total-species RNA balance sensitivity, specificity and interpretability of DE detection, as does filtering likely technical zeros. The efficiency and accuracy of these models pave the way for more effective MTX-based DE discovery in microbial communities.

Availability And Implementation: The analysis code and synthetic datasets used in this evaluation are available online at http://huttenhower.sph.harvard.edu/mtx2021.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275336PMC
July 2021

Dietary fiber intake, the gut microbiome, and chronic systemic inflammation in a cohort of adult men.

Genome Med 2021 Jun 17;13(1):102. Epub 2021 Jun 17.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Background: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

Methods: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of C-reactive protein (CRP), an established biomarker for chronic inflammation. Data were analyzed using multivariate linear mixed models.

Results: We found that inflammation-associated gut microbial configurations corresponded with higher CRP levels. A greater intake of dietary fiber was associated with shifts in gut microbiome composition, particularly Clostridiales, and their potential for carbohydrate utilization via polysaccharide degradation. This was particularly true for fruit fiber sources (i.e., pectin). Most striking, fiber intake was associated with significantly greater CRP reduction in individuals without substantial Prevotella copri carriage in the gut, whereas those with P. copri carriage maintained stable CRP levels regardless of fiber intake.

Conclusions: Our findings offer human evidence supporting a fiber-gut microbiota interaction, as well as a potential specific mechanism by which gut-mediated systemic inflammation may be mitigated.
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http://dx.doi.org/10.1186/s13073-021-00921-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212460PMC
June 2021

Plant-Based Diet Index and Metabolic Risk in Men: Exploring the Role of the Gut Microbiome.

J Nutr 2021 Sep;151(9):2780-2789

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabolic conditions, but its association as well as interactions with microbiome have not been elucidated.

Objectives: We aimed to investigate the interrelations between hPDI, gut microbiome, and cardiometabolic risk markers.

Methods: hPDI was derived from dietary assessments by a validated FFQ and was examined in relation to metagenomic profiles of 911 fecal samples collected from 303 men aged 71 ± 4 y with an average BMI (in kg/m2) of 25.2 ± 3.6 in the Men's Lifestyle Validation Study. Principal coordinate (PCo) analysis based on Bray-Curtis dissimilarity was conducted, and interactions between hPDI and PCo were examined by using a metabolic risk score composed of blood lipids, BMI, and glycated hemoglobin.

Results: After multivariable adjustment, hPDI was significantly associated with the relative abundance of 7 species and 9 pathways. In particular, higher hPDI was significantly associated with a higher relative abundance of Bacteroides cellulosilyticus and Eubacterium eligens, amino acid biosynthesis pathways (l-isoleucine biosynthesis I and III and l-valine biosynthesis), and the pathway of pyruvate fermentation to isobutanol. A favorable association between hPDI and the metabolic risk score was more pronounced among men with a higher PCo characterized by higher abundance of Bacteroides uniformis and lower abundance of Prevotella copri. At the individual species level, a similar interaction was also observed between hPDI and P. copri, as well as with Clostridium clostridioforme or Blautia hydrogenotrophica (all P-interaction < 0.01).

Conclusion: A greater adherence to a healthy plant-based diet by older men was associated with a microbial profile characterized by a higher abundance of multiple species, including B. cellulosilyticus and E. eligens, as well as pathways in amino acid metabolism and pyruvate fermentation. In addition, inverse associations between healthy plant-based diet and human metabolic risk may partially depend on microbial compositions.
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http://dx.doi.org/10.1093/jn/nxab175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417919PMC
September 2021

A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.

Prostate 2021 Jul 6;81(10):683-693. Epub 2021 May 6.

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.

Background: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer).

Methods: Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer. A dense-module-searching method identified modules enriched with significant genes from a genome-wide association study (GWAS) study in a discovery data set, Physicians' Health Study and Health Professionals Follow-up Study (PHS/HPFS). The top 48 candidate single nucleotide polymorphisms (SNPs) from the dense-module-searching method were then assessed in an independent prostate cancer cohort and the one SNP reproducibly associated with lethality was tested in a third cohort. Logistic regression models evaluated the association between each SNP and lethal prostate cancer. The candidate SNP was assessed for association with lethal prostate cancer in 6 of 28 studies in the prostate cancer association group to investigate cancer associated alterations in the genome (PRACTICAL) Consortium where there was some medical record review for death ascertainment which also had SNP data from the ONCOARRAY platform. All men self-identified as Caucasian.

Results: The rs1910301 SNP which was reproducibly associated with lethal disease was nominally associated with lethal disease (odds ratio [OR] = 1.40; p = .02) in the discovery cohort and the minor allele was also associated with lethal disease in two independent cohorts (OR = 1.35; p = .04 and OR = 1.35; p = .07). Fixed effects meta-analysis of all three cohorts found an association: OR = 1.37 (95% confidence interval [CI]: 1.15-1.62, p = .0003). This SNP is in the promoter region of FRAS1, a gene involved in epidermal-basement membrane adhesion and is present at a higher frequency in men with African ancestry. No association was found in the subset of studies from the PRACTICAL consortium studies which had a total of 106 deaths out total of 3263 patients and a median follow-up of 4.4 years.

Conclusions: Through its connection with the NFκB pathway, a candidate SNP with a higher frequency in men of African ancestry without cancer was found to be associated with lethal prostate cancer across three well-annotated independent cohorts of Caucasian men.
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http://dx.doi.org/10.1002/pros.24148DOI Listing
July 2021

Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3.

Elife 2021 May 4;10. Epub 2021 May 4.

Department CIBIO, University of Trento, Trento, Italy.

Culture-independent analyses of microbial communities have progressed dramatically in the last decade, particularly due to advances in methods for biological profiling via shotgun metagenomics. Opportunities for improvement continue to accelerate, with greater access to multi-omics, microbial reference genomes, and strain-level diversity. To leverage these, we present bioBakery 3, a set of integrated, improved methods for taxonomic, strain-level, functional, and phylogenetic profiling of metagenomes newly developed to build on the largest set of reference sequences now available. Compared to current alternatives, MetaPhlAn 3 increases the accuracy of taxonomic profiling, and HUMAnN 3 improves that of functional potential and activity. These methods detected novel disease-microbiome links in applications to CRC (1262 metagenomes) and IBD (1635 metagenomes and 817 metatranscriptomes). Strain-level profiling of an additional 4077 metagenomes with StrainPhlAn 3 and PanPhlAn 3 unraveled the phylogenetic and functional structure of the common gut microbe , previously described by only 15 isolate genomes. With open-source implementations and cloud-deployable reproducible workflows, the bioBakery 3 platform can help researchers deepen the resolution, scale, and accuracy of multi-omic profiling for microbial community studies.
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http://dx.doi.org/10.7554/eLife.65088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096432PMC
May 2021

Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men.

Gut 2021 Apr 29. Epub 2021 Apr 29.

Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA

Objectives: Gut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals.

Design: We collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men's Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features.

Results: TMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO concentrations (false discovery rate <0.05). Higher habitual intake of red meat and choline was significantly associated with higher TMAO concentrations among participants who were microbial TMAO-producers (p<0.05), as characterised based on four abundant TMAO-predicting species, but not among other participants (for red meat=0.003; for choline, =0.03). Among abundant TMAO-predicting species, significantly strengthened the positive association between red meat intake and HbA1c levels (=0.01). Secondary analyses revealed that some functional features, including choline trimethylamine-lyase activating enzymes, were associated with TMAO concentrations.

Conclusion: We identified microbial taxa that were associated with TMAO concentrations and modified the associations of red meat intake with TMAO concentrations and cardiometabolic risk markers. Our data underscore the interplay between diet and gut microbiome in producing potentially bioactive metabolites that may modulate cardiometabolic health.
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http://dx.doi.org/10.1136/gutjnl-2020-322473DOI Listing
April 2021

Overview of the Microbiome Among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies.

Nat Protoc 2021 06 21;16(6):2724-2731. Epub 2021 Apr 21.

Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses' Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort's ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out.
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http://dx.doi.org/10.1038/s41596-021-00519-zDOI Listing
June 2021

A framework for microbiome science in public health.

Nat Med 2021 05 5;27(5):766-774. Epub 2021 Apr 5.

Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.
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http://dx.doi.org/10.1038/s41591-021-01258-0DOI Listing
May 2021

Microbiome Analysis of More Than 2,000 NHS Bowel Cancer Screening Programme Samples Shows the Potential to Improve Screening Accuracy.

Clin Cancer Res 2021 Apr 3;27(8):2246-2254. Epub 2021 Mar 3.

Pathology & Data Analytics, Leeds Institute of Medical Research at St James's University Hospital, University of Leeds, Leeds, United Kingdom.

Purpose: There is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program.

Experimental Design: Between 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes: blood-negative [ = 491 (22%)]; colorectal cancer [ = 430 (19%)]; adenoma [ = 665 (30%)]; colonoscopy-normal [ = 300 (13%)]; nonneoplastic [ = 366 (16%)]. Samples were transported and stored at room temperature. DNA underwent 16S rRNA gene V4 amplicon sequencing. Taxonomic profiling was performed to provide features for classification via random forests (RF).

Results: Samples provided 16S amplicon-based microbial profiles, which confirmed previously described colorectal cancer-microbiome associations. Microbiome-based RF models showed potential as a first-tier screen, distinguishing colorectal cancer or neoplasm (colorectal cancer or adenoma) from blood-negative with AUC 0.86 (0.82-0.89) and AUC 0.78 (0.74-0.82), respectively. Microbiome-based models also showed potential as a second-tier screen, distinguishing from among gFOBT blood-positive samples, colorectal cancer or neoplasm from colonoscopy-normal with AUC 0.79 (0.74-0.83) and AUC 0.73 (0.68-0.77), respectively. Models remained robust when restricted to 15 taxa, and performed similarly during external validation with metagenomic datasets.

Conclusions: Microbiome features can be assessed using gFOBT samples collected and processed routinely by a national colorectal cancer screening program to improve accuracy as a first- or second-tier screen. The models required as few as 15 taxa, raising the potential of an inexpensive qPCR test. This could reduce the number of colonoscopies in countries that use fecal occult blood test screening.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610626PMC
April 2021

Association of with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment.

Clin Cancer Res 2021 May 25;27(10):2816-2826. Epub 2021 Feb 25.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Purpose: While evidence indicates that () may promote colorectal carcinogenesis through its suppressive effect on T-cell-mediated antitumor immunity, the specific T-cell subsets involved remain uncertain.

Experimental Design: We measured DNA within tumor tissue by quantitative PCR on 933 cases (including 128 -positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on , microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages [TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay]. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between and T-cell subsets.

Results: The amount of was inversely associated with tumor stromal CD3 lymphocytes [multivariable OR, 0.47; 95% confidence interval (CI), 0.28-0.79, for -high vs. -negative category; = 0.0004] and specifically stromal CD3CD4CD45RO cells (corresponding multivariable OR, 0.52; 95% CI, 0.32-0.85; = 0.003). These relationships did not substantially differ by MSI status, neoantigen load, or exome-wide tumor mutational burden. was not significantly associated with tumor intraepithelial T cells or with M1 or M2 TAMs.

Conclusions: The amount of tissue is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127352PMC
May 2021

The colorectal cancer-associated faecal microbiome of developing countries resembles that of developed countries.

Genome Med 2021 02 16;13(1):27. Epub 2021 Feb 16.

Pathology & Data Analytics, Leeds Institute of Medical Research at St James's University Hospital, University of Leeds, Level 4 Wellcome Trust Brenner Building, Leeds, LS9 7TF, UK.

Background: The incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a 'resource-light' sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries.

Methods: We assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries. Next, to determine the effect of prolonged UK storage, DNA extraction replicates for a subset of samples were performed up to 252 days apart. To profile the CRC-associated microbiome of developing countries, gFOBT were collected from 41 treatment-naïve CRC patients and 40 non-CRC controls from across the four institutes, and V4 16S rRNA gene sequencing was performed. Finally, we constructed a random forest (RF) model that was trained and tested against existing datasets from developed countries.

Results: The microbiome was stably assayed when samples were stored/transported at room temperature and after prolonged UK storage. Large-scale microbiome structure was separated by country and continent, with a smaller effect from CRC. Importantly, the RF model performed similarly to models trained using external datasets and identified similar taxa of importance (Parvimonas, Peptostreptococcus, Fusobacterium, Alistipes, and Escherichia).

Conclusions: This study demonstrates that gFOBT, stored and transported at room temperature, represents a suitable method of faecal sample collection for amplicon-based microbiome biomarkers in developing countries and suggests a CRC-faecal microbiome association that is consistent between developed and developing countries.
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http://dx.doi.org/10.1186/s13073-021-00844-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887780PMC
February 2021

The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk.

Nat Med 2021 02 11;27(2):333-343. Epub 2021 Feb 11.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.
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http://dx.doi.org/10.1038/s41591-020-01223-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186452PMC
February 2021

Triclosan Tolerance Is Driven by a Conserved Mechanism in Diverse Species.

Appl Environ Microbiol 2021 03 11;87(7). Epub 2021 Mar 11.

Department of Civil and Environmental Engineering, Northwestern University, Evanston, Illinois, USA

Perturbation of natural microbial communities by antimicrobials, such as triclosan, can result in selection for antibiotic tolerance, which is of particular concern when pathogens are present. Members of the genus are found in many natural microbial communities and frequently demonstrate increased abundance following triclosan exposure. The pathogen and well-studied model organism exhibits high triclosan tolerance; however, it is unknown if all species share this trait or if there are susceptible strains. We characterized the triclosan tolerance phenotypes of diverse isolates obtained from triclosan-exposed built environments and identified both tolerant and sensitive strains. High tolerance is associated with carriage of the enoyl-acyl carrier reductase (ENR) isozyme gene , compared to the lesser protective effects of efflux or presence of ENRs. Given its unique importance, we examined distribution throughout species using large-scale phylogenomic analyses. We find presence or absence is largely invariant at the species level but demonstrates multiple gain and loss events in its evolutionary history. We further provide evidence of its presence on mobile genetic elements. Our results demonstrate the surprising variability in triclosan tolerance in and confirm to be a useful indicator for high triclosan tolerance in These findings provide a framework for better monitoring of in triclosan-exposed environments and interpreting effects on species and gene composition. Closely related species are typically assumed to demonstrate similar phenotypes driven by underlying conserved genotypes. When monitoring for the effect of antimicrobials on the types of species that may be selected for, this assumption may prove to be incorrect, and identification of additional genetic markers may be necessary. We isolated several phylogenetically diverse members of from indoor environments and tested their phenotypic tolerance toward the commonly used antimicrobial triclosan. Although isolates are broadly regarded to be highly triclosan tolerant, we demonstrate the presence of both triclosan-tolerant and -susceptible strains, separated by a difference in tolerance of nearly 3 orders of magnitude. Bioinformatic and experimental investigation demonstrated that the presence of the gene was associated with high tolerance. We demonstrate that is not evenly distributed in all species and that its presence could be a useful predictor of high triclosan tolerance suitable for antimicrobial monitoring efforts involving triclosan.
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http://dx.doi.org/10.1128/AEM.02924-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091609PMC
March 2021

Whole microbial community viability is not quantitatively reflected by propidium monoazide sequencing approach.

Microbiome 2021 01 21;9(1):17. Epub 2021 Jan 21.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 655 Huntington Avenue, Boston, MA, 02115, USA.

Background: High-throughput sequencing provides a powerful window into the structural and functional profiling of microbial communities, but it is unable to characterize only the viable portion of microbial communities at scale. There is as yet not one best solution to this problem. Previous studies have established viability assessments using propidium monoazide (PMA) treatment coupled with downstream molecular profiling (e.g., qPCR or sequencing). While these studies have met with moderate success, most of them focused on the resulting "viable" communities without systematic evaluations of the technique. Here, we present our work to rigorously benchmark "PMA-seq" (PMA treatment followed by 16S rRNA gene amplicon sequencing) for viability assessment in synthetic and realistic microbial communities.

Results: PMA-seq was able to successfully reconstruct simple synthetic communities comprising viable/heat-killed Escherichia coli and Streptococcus sanguinis. However, in realistically complex communities (computer screens, computer mice, soil, and human saliva) with E. coli spike-in controls, PMA-seq did not accurately quantify viability (even relative to variability in amplicon sequencing), with its performance largely affected by community properties such as initial biomass, sample types, and compositional diversity. We then applied this technique to environmental swabs from the Boston subway system. Several taxa differed significantly after PMA treatment, while not all microorganisms responded consistently. To elucidate the "PMA-responsive" microbes, we compared our results with previous PMA-based studies and found that PMA responsiveness varied widely when microbes were sourced from different ecosystems but were reproducible within similar environments across studies.

Conclusions: This study provides a comprehensive evaluation of PMA-seq exploring its quantitative potential in synthetic and complex microbial communities, where the technique was effective for semi-quantitative purposes in simple synthetic communities but provided only qualitative assessments in realistically complex community samples. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00961-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819323PMC
January 2021

Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals.

Nat Med 2021 02 11;27(2):321-332. Epub 2021 Jan 11.

Zoe Global Ltd, London, UK.

The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.
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http://dx.doi.org/10.1038/s41591-020-01183-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353542PMC
February 2021

Delivery Mode Affects Stability of Early Infant Gut Microbiota.

Cell Rep Med 2020 Dec 22;1(9):100156. Epub 2020 Dec 22.

Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91121, Israel.

Mode of delivery strongly influences the early infant gut microbiome. Children born by cesarean section (C-section) lack species until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome. Here, we re-evaluate this hypothesis by comparing the microbial profiles of 75 infants born vaginally or by planned versus emergent C-section. Multiple children born by C-section have a high abundance of in their first few days of life, but at 2 weeks, both C-section groups lack (primarily according to 16S sequencing), despite their difference in exposure to the birth canal. Finally, a comparison of microbial strain profiles between infants and maternal vaginal or rectal samples finds evidence for mother-to-child transmission of rectal rather than vaginal strains. These results suggest differences in colonization stability as an important factor in infant gut microbiome composition rather than birth canal exposure.
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http://dx.doi.org/10.1016/j.xcrm.2020.100156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762768PMC
December 2020

Determinants of Staphylococcus aureus carriage in the developing infant nasal microbiome.

Genome Biol 2020 12 11;21(1):301. Epub 2020 Dec 11.

Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.

Background: Staphylococcus aureus is a leading cause of healthcare- and community-associated infections and can be difficult to treat due to antimicrobial resistance. About 30% of individuals carry S. aureus asymptomatically in their nares, a risk factor for later infection, and interactions with other species in the nasal microbiome likely modulate its carriage. It is thus important to identify ecological or functional genetic elements within the maternal or infant nasal microbiomes that influence S. aureus acquisition and retention in early life.

Results: We recruited 36 mother-infant pairs and profiled a subset of monthly longitudinal nasal samples from the first year after birth using shotgun metagenomic sequencing. The infant nasal microbiome is highly variable, particularly within the first 2 months. It is weakly influenced by maternal nasal microbiome composition, but primarily shaped by developmental and external factors, such as daycare. Infants display distinctive patterns of S. aureus carriage, positively associated with Acinetobacter species, Streptococcus parasanguinis, Streptococcus salivarius, and Veillonella species and inversely associated with maternal Dolosigranulum pigrum. Furthermore, we identify a gene family, likely acting as a taxonomic marker for an unclassified species, that is significantly anti-correlated with S. aureus in infants and mothers. In gene content-based strain profiling, infant S. aureus strains are more similar to maternal strains.

Conclusions: This improved understanding of S. aureus colonization is an important first step toward the development of novel, ecological therapies for controlling S. aureus carriage.
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http://dx.doi.org/10.1186/s13059-020-02209-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731505PMC
December 2020

Microbiome Biomarkers: One Step Closer in NAFLD Cirrhosis.

Hepatology 2021 May 19;73(5):2063-2066. Epub 2021 Apr 19.

Broad Institute, Boston, MA.

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http://dx.doi.org/10.1002/hep.31660DOI Listing
May 2021

Identification of Natural CRISPR Systems and Targets in the Human Microbiome.

Cell Host Microbe 2021 01 19;29(1):94-106.e4. Epub 2020 Nov 19.

Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address:

Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes, yielding functional and taxonomic profiles for 2.9 million spacers by aligning the spacer content to each sample's metagenome and corresponding gene families. Spacer and repeat profiles agree qualitatively with those from isolate genomes but expand their diversity by approximately 13-fold, with the highest spacer load present in the oral microbiome. The taxonomy of spacer sequences parallels that of their source community, with functional targets enriched for viral elements. When coupled with cas gene systems, CRISPR-Cas subtypes are highly site and taxon specific. Our analysis provides a comprehensive collection of natural CRISPR-cas loci and targets in the human microbiome.
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http://dx.doi.org/10.1016/j.chom.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813156PMC
January 2021

The human gut microbiota in people with amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener 2021 05 2;22(3-4):186-194. Epub 2020 Nov 2.

Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.

Objective: To characterize the gut microbiota in people with amyotrophic lateral sclerosis (ALS) relative to controls and to test the hypothesis that butyrate-producing bacteria are less abundant in the gastrointestinal tracts of people with ALS (PALS). We conducted a case-control study at Massachusetts General Hospital to compare the gut microbiota in people with ALS to that in controls. Metagenomic shotgun sequencing was performed on DNA extracted from stool samples of 66 people with ALS (PALS), 61 healthy controls (HC), and 12 neurodegenerative controls (NDC). Taxonomic metagenomic profiles were analyzed for shifts in the microbial community structure between the comparator groups using per-feature univariate and multivariate association tests. The relative abundance of the dominant butyrate-producing bacteria and was significantly lower in ALS patients compared to HC. Adjustment for age, sex, and constipation did not materially change the results. The total abundance of 8 dominant species capable of producing butyrate was also significantly lower in ALS compared to HC (p < 0.001). The levels of several butyrate-producing bacteria, which are important for gut integrity and regulation of inflammation, were lower in people with ALS compared to controls. These findings lend support to the inference that the gut microbiota could be a risk factor for ALS. Further investigations are warranted, preferably earlier in the disease with corresponding dietary collection and a longitudinal design.
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http://dx.doi.org/10.1080/21678421.2020.1828475DOI Listing
May 2021

Strain-level epidemiology of microbial communities and the human microbiome.

Genome Med 2020 08 13;12(1):71. Epub 2020 Aug 13.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.

The biological importance and varied metabolic capabilities of specific microbial strains have long been established in the scientific community. Strains have, in the past, been largely defined and characterized based on microbial isolates. However, the emergence of new technologies and techniques has enabled assessments of their ecology and phenotypes within microbial communities and the human microbiome. While it is now more obvious how pathogenic strain variants are detrimental to human health, the consequences of subtle genetic variation in the microbiome have only recently been exposed. Here, we review the operational definitions of strains (e.g., genetic and structural variants) as they can now be identified from microbial communities using different high-throughput, often culture-independent techniques. We summarize the distribution and diversity of strains across the human body and their emerging links to health maintenance, disease risk and progression, and biochemical responses to perturbations, such as diet or drugs. We list methods for identifying, quantifying, and tracking strains, utilizing high-throughput sequencing along with other molecular and "culturomics" technologies. Finally, we discuss implications of population studies in bridging experimental gaps and leading to a better understanding of the health effects of strains in the human microbiome.
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http://dx.doi.org/10.1186/s13073-020-00765-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427293PMC
August 2020

A Phase 1b Safety Study of SER-287, a Spore-Based Microbiome Therapeutic, for Active Mild to Moderate Ulcerative Colitis.

Gastroenterology 2021 01 4;160(1):115-127.e30. Epub 2020 Aug 4.

Seres Therapeutics, Cambridge, Massachusetts.

Background & Aims: Firmicutes bacteria produce metabolites that maintain the intestinal barrier and mucosal immunity. Firmicutes are reduced in the intestinal microbiota of patients with ulcerative colitis (UC). In a phase 1b trial of patients with UC, we evaluated the safety and efficacy of SER-287, an oral formulation of Firmicutes spores, and the effects of vancomycin preconditioning on expansion (engraftment) of SER-287 species in the colon.

Methods: We conducted a double-blind trial of SER-287 in 58 adults with active mild-to-moderate UC (modified Mayo scores 4-10, endoscopic subscores ≥1). Participants received 6 days of preconditioning with oral vancomycin (125 mg, 4 times daily) or placebo followed by 8 weeks of oral SER-287 or placebo. Patients were randomly assigned (2:3:3:3) to groups that received placebo followed by either placebo or SER-287 once weekly, or vancomycin followed by SER-287 once weekly, or SER-287 once daily. Clinical end points included safety and clinical remission (modified Mayo score ≤2; endoscopic subscores 0 or 1). Microbiome end points included SER-287 engraftment (dose species detected in stool after but not before SER-287 administration). Engraftment of SER-287 and changes in microbiome composition and associated metabolites were measured by analyses of stool specimens collected at baseline, after preconditioning, and during and 4 weeks after administration of SER-287 or placebo.

Results: Proportions of patients with adverse events did not differ significantly among groups. A higher proportion of patients in the vancomycin/SER-287 daily group (40%) achieved clinical remission at week 8 than patients in the placebo/placebo group (0%), placebo/SER-287 weekly group (13.3%), or vancomycin/SER-287 weekly group (17.7%) (P = .024 for vancomycin/SER-287 daily vs placebo/placebo). By day 7, higher numbers of SER-287 dose species were detected in stool samples from all SER-287 groups compared with the placebo group (P < .05), but this difference was not maintained beyond day 7 in the placebo/SER-287 weekly group. In the vancomycin groups, a greater number of dose species were detected in stool collected on day 10 and all subsequent time points through 4 weeks post dosing compared with the placebo group (P < .05). A higher number of SER-287 dose species were detected in stool samples on days 7 and 10 from subjects who received daily vs weekly SER-287 doses (P < .05). Changes in fecal microbiome composition and metabolites were associated with both vancomycin/SER-287 groups.

Conclusions: In this small phase 1b trial of limited duration, the safety and tolerability of SER-287 were similar to placebo. SER-287 after vancomycin was significantly more effective than placebo for induction of remission in patients with active mild to moderate UC. Engraftment of dose species was facilitated by vancomycin preconditioning and daily dosing of SER-287. ClinicalTrials.gov ID NCT02618187.
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http://dx.doi.org/10.1053/j.gastro.2020.07.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402096PMC
January 2021

Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations.

Genome Biol 2020 06 8;21(1):138. Epub 2020 Jun 8.

Department CIBIO, University of Trento, Trento, Italy.

Background: Eubacterium rectale is one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome investigations of this microbe have not been carried out.

Results: Here, we leverage metagenomic assembly followed by a reference-based binning strategy to screen over 6500 gut metagenomes spanning geography and lifestyle and reconstruct over 1300 E. rectale high-quality genomes from metagenomes. We extend previous results of biogeographic stratification, identifying a new subspecies predominantly found in African individuals and showing that closely related non-human primates do not harbor E. rectale. Comparison of pairwise genetic and geographic distances between subspecies suggests that isolation by distance and co-dispersal with human populations might have contributed to shaping the contemporary population structure of E. rectale. We confirm that a relatively recently diverged E. rectale subspecies specific to Europe consistently lacks motility operons and that it is immotile in vitro, probably due to ancestral genetic loss. The same subspecies exhibits expansion of its carbohydrate metabolism gene repertoire including the acquisition of a genomic island strongly enriched in glycosyltransferase genes involved in exopolysaccharide synthesis.

Conclusions: Our study provides new insights into the population structure and ecology of E. rectale and shows that shotgun metagenomes can enable population genomics studies of microbiota members at a resolution and scale previously attainable only by extensive isolate sequencing.
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http://dx.doi.org/10.1186/s13059-020-02042-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278147PMC
June 2020
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