Publications by authors named "Dan Knights"

107 Publications

Placentas delivered by pre-pregnant obese women have reduced abundance and diversity in the microbiome.

FASEB J 2021 Apr;35(4):e21524

Department of Computational Medicine and Bioinformatics, North Campus Research Complex, University of Michigan, Ann Arbor, MI, USA.

Maternal pre-pregnancy obesity may have an impact on both maternal and fetal health. We examined the microbiome recovered from placentas in a multi-ethnic maternal pre-pregnant obesity cohort, through an optimized microbiome protocol to enrich low bacterial biomass samples. We found that the microbiomes recovered from the placentas of obese pre-pregnant mothers are less abundant and less diverse when compared to those from mothers of normal pre-pregnancy weight. Microbiome richness also decreases from the maternal side to the fetal side, demonstrating heterogeneity by geolocation within the placenta. In summary, our study shows that the microbiomes recovered from the placentas are associated with pre-pregnancy obesity. IMPORTANCE: Maternal pre-pregnancy obesity may have an impact on both maternal and fetal health. The placenta is an important organ at the interface of the mother and fetus, and supplies nutrients to the fetus. We report that the microbiomes enriched from the placentas of obese pre-pregnant mothers are less abundant and less diverse when compared to those from mothers of normal pre-pregnancy weight. More over, the microbiomes also vary by geolocation within the placenta.
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http://dx.doi.org/10.1096/fj.202002184RRDOI Listing
April 2021

Wild primate microbiomes prevent weight gain in germ-free mice.

Anim Microbiome 2020 May 7;2(1):16. Epub 2020 May 7.

Biotechnology Institute, University of Minnesota, 1479 Gortner Avenue, Saint Paul, MN, 55108, USA.

Background: The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined.

Results: To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice.

Conclusions: In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet.
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http://dx.doi.org/10.1186/s42523-020-00033-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807445PMC
May 2020

Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation.

Sci Transl Med 2020 11;12(571)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO). These animals exhibited increased gut permeability, endotoxin translocation across the gut, and radiation-induced gastrointestinal damage after allo-HSCT. After allo-HSCT, both male and female DIO mouse recipients showed increased proinflammatory cytokine production and expression of the GVHD marker ST2 (IL-33R) and MHC class II molecules; they also exhibited decreased survival associated with acute severe gut GVHD. This rapid-onset, obesity-associated gut GVHD depended on donor CD4 T cells and occurred even with a minor MHC mismatch between donor and recipient animals. Retrospective analysis of clinical cohorts receiving allo-HSCT transplants from unrelated donors revealed that recipients with a high body mass index (BMI, >30) had reduced survival and higher serum ST2 concentrations compared with nonobese transplant recipients. Assessment of both DIO mice and allo-HSCT recipients with a high BMI revealed reduced gut microbiota diversity and decreased Clostridiaceae abundance. Prophylactic antibiotic treatment protected DIO mouse recipients from endotoxin translocation across the gut and increased inflammatory cytokine production, as well as gut pathology and mortality, but did not protect against later development of chronic skin GVHD. These results suggest that obesity-induced alterations of the gut microbiota may affect GVHD after allo-HSCT in DIO mice, which could be ameliorated by prophylactic antibiotic treatment.
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http://dx.doi.org/10.1126/scitranslmed.aay7713DOI Listing
November 2020

Metagenomic Information Recovery from Human Stool Samples Is Influenced by Sequencing Depth and Profiling Method.

Genes (Basel) 2020 Nov 21;11(11). Epub 2020 Nov 21.

Diversigen Inc., Houston, TX 77021, USA.

Sequencing of the 16S rRNA gene (16S) has long been a go-to method for microbiome characterization due to its accessibility and lower cost compared to shotgun metagenomic sequencing (SMS). However, 16S sequencing rarely provides species-level resolution and cannot provide direct assessment of other taxa (e.g., viruses and fungi) or functional gene content. Shallow shotgun metagenomic sequencing (SSMS) has emerged as an approach to bridge the gap between 16S sequencing and deep metagenomic sequencing. SSMS is cost-competitive with 16S sequencing, while also providing species-level resolution and functional gene content insights. In the present study, we evaluated the effects of sequencing depth on marker gene-mapping- and alignment-based annotation of bacteria in healthy human stool samples. The number of identified taxa decreased with lower sequencing depths, particularly with the marker gene-mapping-based approach. Other annotations, including viruses and pathways, also showed a depth-dependent effect on feature recovery. These results refine the understanding of the suitability and shortcomings of SSMS, as well as annotation tools for metagenomic analyses in human stool samples. Results may also translate to other sample types and may open the opportunity to explore the effect of sequencing depth and annotation method.
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http://dx.doi.org/10.3390/genes11111380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700633PMC
November 2020

A Potential Role for Stress-Induced Microbial Alterations in IgA-Associated Irritable Bowel Syndrome with Diarrhea.

Cell Rep Med 2020 Oct;1(7)

Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, this process is not well understood. Here, we find that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via the opening of goblet-cell associated passages. Notably, stress increases host immunity to gut bacteria as assessed by immunoglobulin A (IgA)-bound gut bacteria. Stress-induced microbial changes are necessary and sufficient to elicit these effects. Moreover, similar to mice, many diarrhea-predominant IBS (IBS-D) patients from two cohorts display increased antibacterial immunity as assessed by IgA-bound fecal bacteria. This antibacterial IgA response in IBS-D correlates with somatic symptom severity and was distinct from healthy controls or IBD patients. These findings suggest that stress may play an important role in patients with IgA-associated IBS-D by disrupting the intestinal microbial community that alters gastrointestinal function and host immunity to commensal bacteria.
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http://dx.doi.org/10.1016/j.xcrm.2020.100124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659537PMC
October 2020

Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy.

Gut 2020 Sep 30. Epub 2020 Sep 30.

Microbiome Analysis Center, George Mason University, Manassas, Virginia, USA.

Objective: Altered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear.

Design: Cross-sectional and pre/post rifaximin cohorts were enrolled. Cross-sectional: controls and cirrhotic outpatients (compensated, on lactulose (Cirr-L), on rifaximin (Cirr-LR)) were included and followed for 90-day hospitalisations. Pre/post: compensated cirrhotics underwent stool collection pre/post 8 weeks of rifaximin. Stool metagenomics for bacteria and phages and their correlation networks were analysed in controls versus cirrhosis, within cirrhotics, hospitalised/not and pre/post rifaximin.

Results: Cross-sectional: 40 controls and 163 cirrhotics (63 compensated, 43 Cirr-L, 57 Cirr-LR) were enrolled. Cirr-L/LR groups were similar on model for end-stage liver disease (MELD) score but Cirr-L developed greater hospitalisations versus Cirr-LR (56% vs 30%, p=0.008). Bacterial alpha/beta diversity worsened from controls through Cirr-LR. While phage alpha diversity was similar, beta diversity was different between groups. Autochthonous bacteria linked negatively, pathobionts linked positively with MELD but only modest phage-MELD correlations were seen. Phage-bacterial correlation network complexity was highest in controls, lowest in Cirr-L and increased in Cirr-LR. and phages were linked with autochthonous bacteria in Cirr-LR, but not Cirr-L hospitalised patients had greater pathobionts, lower commensal bacteria and phages focused on and Myoviridae. Pre/post: No changes in alpha/beta diversity of phages or bacteria were seen postrifaximin. Phage-bacterial linkages centred around urease-producing species collapsed postrifaximin.

Conclusion: Unlike bacteria, faecal phages are sparsely linked with cirrhosis characteristics and 90-day outcomes. Phage and bacterial linkages centred on urease-producing, ammonia-generating species were affected by disease progression and rifaximin therapy and were altered in patients who experienced 90-day hospitalisations.
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http://dx.doi.org/10.1136/gutjnl-2020-322470DOI Listing
September 2020

Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome.

Cell 2020 Sep 10;182(6):1460-1473.e17. Epub 2020 Sep 10.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2020.08.007DOI Listing
September 2020

Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.

Gastroenterology 2021 Jan 26;160(1):158-173.e10. Epub 2020 Aug 26.

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Harvard T.H. Chan School of Public Health, Cambridge, Massachusetts. Electronic address:

Background & Aims: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase.

Methods: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet.

Results: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, -1.46 ± 3.6 μIU/mL vs placebo, 1.64 ± 4.7 μIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05).

Conclusions: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.
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http://dx.doi.org/10.1053/j.gastro.2020.08.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755729PMC
January 2021

Gut microbiota modulation with long-chain corn bran arabinoxylan in adults with overweight and obesity is linked to an individualized temporal increase in fecal propionate.

Microbiome 2020 08 19;8(1):118. Epub 2020 Aug 19.

Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada.

Background: Variability in the health effects of dietary fiber might arise from inter-individual differences in the gut microbiota's ability to ferment these substrates into beneficial metabolites. Our understanding of what drives this individuality is vastly incomplete and will require an ecological perspective as microbiomes function as complex inter-connected communities. Here, we performed a parallel two-arm, exploratory randomized controlled trial in 31 adults with overweight and class-I obesity to characterize the effects of long-chain, complex arabinoxylan (n = 15) at high supplementation doses (female: 25 g/day; male: 35 g/day) on gut microbiota composition and short-chain fatty acid production as compared to microcrystalline cellulose (n = 16, non-fermentable control), and integrated the findings using an ecological framework.

Results: Arabinoxylan resulted in a global shift in fecal bacterial community composition, reduced α-diversity, and the promotion of specific taxa, including operational taxonomic units related to Bifidobacterium longum, Blautia obeum, and Prevotella copri. Arabinoxylan further increased fecal propionate concentrations (p = 0.012, Friedman's test), an effect that showed two distinct groupings of temporal responses in participants. The two groups showed differences in compositional shifts of the microbiota (p ≤ 0.025, PERMANOVA), and multiple linear regression (MLR) analyses revealed that the propionate response was predictable through shifts and, to a lesser degree, baseline composition of the microbiota. Principal components (PCs) derived from community data were better predictors in MLR models as compared to single taxa, indicating that arabinoxylan fermentation is the result of multi-species interactions within microbiomes.

Conclusion: This study showed that long-chain arabinoxylan modulates both microbiota composition and the output of health-relevant SCFAs, providing information for a more targeted application of this fiber. Variation in propionate production was linked to both compositional shifts and baseline composition, with PCs derived from shifts of the global microbial community showing the strongest associations. These findings constitute a proof-of-concept for the merit of an ecological framework that considers features of the wider gut microbial community for the prediction of metabolic outcomes of dietary fiber fermentation. This provides a basis to personalize the use of dietary fiber in nutritional application and to stratify human populations by relevant gut microbiota features to account for the inconsistent health effects in human intervention studies.

Trial Registration: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00887-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439537PMC
August 2020

Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk.

Aliment Pharmacol Ther 2020 09 8;52(6):976-987. Epub 2020 Aug 8.

Minneapolis, MN, USA.

Background: Aspirin is associated with decreased risk of colorectal cancer (CRC), potentially by modulating the gut microbiome.

Aims: To evaluate the effect of aspirin on the gut microbiome in a double-blinded, randomised placebo-controlled pilot trial.

Methods: Healthy volunteers aged 50-75 received a standard dose of aspirin (325 mg, N = 30) or placebo (N = 20) once daily for 6 weeks and provided stool samples every 3 weeks for 12 weeks. Serial measurements of gut microbial community composition and bacterial abundance were derived from 16S rRNA sequences. Linear discriminant analysis of effect size (LEfSe) was tested for between-arm differences in bacterial abundance. Mixed-effect regression with binomial distribution estimated the effect of aspirin use on changes in the relative abundance of individual bacterial taxa via an interaction term (treatment × time).

Results: Over the study period, there were differences in microbial composition in the aspirin vs placebo arm. After treatment, four taxa were differentially abundant across arms: Prevotella, Veillonella, Clostridium XlVa and Clostridium XVIII clusters. Of pre-specified bacteria associated with CRC (n = 8) or aspirin intake (n = 4) in published studies, interactions were significant for four taxa, suggesting relative increases in Akkermansia, Prevotella and Ruminococcaceae and relative decreases in Parabacteroides, Bacteroides and Dorea in the aspirin vs placebo arm.

Conclusion: Compared to placebo, aspirin intake influenced several microbial taxa (Ruminococcaceae, Clostridium XlVa, Parabacteroides and Dorea) in a direction consistent with a priori hypothesis based on their association with CRC. This suggests that aspirin may influence CRC development through an effect on the gut microbiome. The findings need replication in a larger trial.
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http://dx.doi.org/10.1111/apt.16013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719064PMC
September 2020

A Guide to Diet-Microbiome Study Design.

Front Nutr 2020 12;7:79. Epub 2020 Jun 12.

Department of Nutrition, University of California, Davis, Davis, CA, United States.

Intense recent interest in understanding how the human gut microbiome influences health has kindled a concomitant interest in linking dietary choices to microbiome variation. Diet is known to be a driver of microbiome variation, and yet the precise mechanisms by which certain dietary components modulate the microbiome, and by which the microbiome produces byproducts and secondary metabolites from dietary components, are not well-understood. Interestingly, despite the influence of diet on the gut microbiome, the majority of microbiome studies published to date contain little or no analysis of dietary intake. Although an increasing number of microbiome studies are now collecting some form of dietary data or even performing diet interventions, there are no clear standards in the microbiome field for how to collect diet data or how to design a diet-microbiome study. In this article, we review the current practices in diet-microbiome analysis and study design and make several recommendations for best practices to provoke broader discussion in the field. We recommend that microbiome studies include multiple consecutive microbiome samples per study timepoint or phase and multiple days of dietary history prior to each microbiome sample whenever feasible. We find evidence that direct effects of diet on the microbiome are likely to be observable within days, while the length of an intervention required for observing microbiome-mediated effects on the host phenotype or host biomarkers, depending on the outcome, may be much longer, on the order of weeks or months. Finally, recent studies demonstrating that diet-microbiome interactions are personalized suggest that diet-microbiome studies should either include longitudinal sampling within individuals to identify personalized responses, or should include an adequate number of participants spanning a range of microbiome types to identify generalized responses.
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http://dx.doi.org/10.3389/fnut.2020.00079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303276PMC
June 2020

SHOGUN: a modular, accurate and scalable framework for microbiome quantification.

Bioinformatics 2020 07;36(13):4088-4090

Department of Computer Science and Engineering, University of Minnesota, Minneapolis, 55455 Minnesota, USA.

Summary: The software pipeline SHOGUN profiles known taxonomic and gene abundances of short-read shotgun metagenomics sequencing data. The pipeline is scalable, modular and flexible. Data analysis and transformation steps can be run individually or together in an automated workflow. Users can easily create new reference databases and can select one of three DNA alignment tools, ranging from ultra-fast low-RAM k-mer-based database search to fully exhaustive gapped DNA alignment, to best fit their analysis needs and computational resources. The pipeline includes an implementation of a published method for taxonomy assignment disambiguation with empirical Bayesian redistribution. The software is installable via the conda resource management framework, has plugins for the QIIME2 and QIITA packages and produces both taxonomy and gene abundance profile tables with a single command, thus promoting convenient and reproducible metagenomics research.

Availability And Implementation: https://github.com/knights-lab/SHOGUN.
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http://dx.doi.org/10.1093/bioinformatics/btaa277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359755PMC
July 2020

Sex Bias in Gut Microbiome Transmission in Newly Paired Marmosets (Callithrix jacchus).

mSystems 2020 Mar 24;5(2). Epub 2020 Mar 24.

Department of Biology, University of Nebraska at Omaha, Omaha, Nebraska, USA.

Social behavior can alter the microbiome composition via transmission among social partners, but there have been few controlled experimental studies of gut microbiome transmission among social partners in primates. We collected longitudinal fecal samples from eight unrelated male-female pairs of marmoset monkeys prior to pairing and for 8 weeks following pairing. We then sequenced 16S rRNA to characterize the changes in the gut microbiome that resulted from the pairing. Marmoset pairs had a higher similarity in gut microbiome communities after pairing than before pairing. We discovered sex differences in the degrees of change in gut microbiome communities following pairing. Specifically, the gut microbiome communities in males exhibited greater dissimilarity from the prepairing stage (baseline) than the gut microbiome communities in females. Conversely, females showed a gradual stabilization in the rate of the gut microbiome community turnover. Importantly, we found that the male fecal samples harbored more female-source gut microbes after pairing, especially early in pairing (paired test, 0.05), possibly linked to sex bias in the frequencies of social behavior. From this controlled study, we report for the first time that pair-living primates undergo significant changes in gut microbiome during pairing and that females transmit more microbes to their partners than males do. The potential biases influencing which microbes are transmitted on the basis of sex and whether they are due to sex biases in other behavioral or physiological features need to be widely investigated in other nonhuman primates and humans in the future. In this controlled study, we collected longitudinal fecal samples from 16 male and female marmoset monkeys for 2 weeks prior to and for 8 weeks after pairing in male-female dyads. We report for the first time that marmoset monkeys undergo significant changes to the gut microbiome following pairing and that these changes are sex-biased; i.e., females transmit more microbes to their social partners than males do. Marmosets exhibit pair bonding behavior such as spatial proximity, physical contact, and grooming, and sex biases in these behavioral patterns may contribute to the observed sex bias in social transmission of gut microbiomes.
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http://dx.doi.org/10.1128/mSystems.00910-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093826PMC
March 2020

Phylogenomics of 10,575 genomes reveals evolutionary proximity between domains Bacteria and Archaea.

Nat Commun 2019 12 2;10(1):5477. Epub 2019 Dec 2.

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.

Rapid growth of genome data provides opportunities for updating microbial evolutionary relationships, but this is challenged by the discordant evolution of individual genes. Here we build a reference phylogeny of 10,575 evenly-sampled bacterial and archaeal genomes, based on a comprehensive set of 381 markers, using multiple strategies. Our trees indicate remarkably closer evolutionary proximity between Archaea and Bacteria than previous estimates that were limited to fewer "core" genes, such as the ribosomal proteins. The robustness of the results was tested with respect to several variables, including taxon and site sampling, amino acid substitution heterogeneity and saturation, non-vertical evolution, and the impact of exclusion of candidate phyla radiation (CPR) taxa. Our results provide an updated view of domain-level relationships.
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http://dx.doi.org/10.1038/s41467-019-13443-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889312PMC
December 2019

US Immigration Is Associated With Rapid and Persistent Acquisition of Antibiotic Resistance Genes in the Gut.

Clin Infect Dis 2020 07;71(2):419-421

MiHAR Laboratory, Université de Nantes, Nantes, France.

Little is known about the effect of human migration on gut microbiome antibiotic resistance gene (ARG) carriage. Using deep shotgun stool metagenomics analysis, we found a rapid increase in gut microbiome ARG richness and abundance in women from 2 independent ethnic groups relocating from Thailand to the United States.
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http://dx.doi.org/10.1093/cid/ciz1087DOI Listing
July 2020

Antibiotics and Host-Tailored Probiotics Similarly Modulate Effects on the Developing Avian Microbiome, Mycobiome, and Host Gene Expression.

mBio 2019 10 15;10(5). Epub 2019 Oct 15.

Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota, USA

The microbiome is important to all animals, including poultry, playing a critical role in health and performance. Low-dose antibiotics have historically been used to modulate food production animals and their microbiome. Identifying alternatives to antibiotics conferring similar modulatory properties has been elusive. The purpose of this study was to determine if a host-tailored probiotic could recapitulate effects of a low-dose antibiotic on host response and the developing microbiome. Over 13 days of life, turkey poults were supplemented continuously with a low-dose antibiotic or oral supplementation of a prebiotic with or without two different probiotics (8 cage units,  = 80 per group). Gastrointestinal bacterial and fungal communities of poults were characterized by 16S rRNA gene and ITS2 amplicon sequencing. Localized and systemic host gene expression was assessed using transcriptome sequencing (RNA-Seq), kinase activity was assessed by avian-specific kinome peptide arrays, and performance parameters were assessed. We found that development of the early-life microbiome of turkey poults was tightly ordered in a tissue- and time-specific manner. Low-dose antibiotic and turkey-tailored probiotic supplementation, but not nontailored probiotic supplementation, elicited similar shifts in overall microbiome composition during development compared to controls. Treatment-induced bacterial changes were accompanied by parallel shifts in the fungal community and host gene expression and enhanced performance metrics. These results were validated in pen trials that identified further additive effects of the turkey-tailored probiotic combined with different prebiotics. Alternative approaches to low-dose antibiotic use in poultry are feasible and can be optimized utilizing the indigenous poultry microbiome. Similar approaches may also be beneficial for humans. Alternative approaches are greatly needed to reduce the need for antibiotic use in food animal production. This study utilized a pipeline for the development of a host-tailored probiotic to enhance performance in commercial turkeys and modulate their microbiota, similar to the effects of low-dose antibiotic administration. We determined that a host-tailored probiotic, developed in the context of the commercial turkey gut microbiome, was more effective at modulating these parameters than a nontailored probiotic cocktail. Furthermore, the host-tailored probiotic mimicked many of the effects of a low-dose antibiotic growth promoter. Surprisingly, the effects of the antibiotic growth promoter and host-tailored probiotic were observed across kingdoms, illustrating the coordinated interkingdom effects of these approaches. This work suggests that tailored approaches to probiotic development hold promise for modulating the avian host and its microbiota.
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http://dx.doi.org/10.1128/mBio.02171-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794479PMC
October 2019

Author Correction: Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.

Authors:
Evan Bolyen Jai Ram Rideout Matthew R Dillon Nicholas A Bokulich Christian C Abnet Gabriel A Al-Ghalith Harriet Alexander Eric J Alm Manimozhiyan Arumugam Francesco Asnicar Yang Bai Jordan E Bisanz Kyle Bittinger Asker Brejnrod Colin J Brislawn C Titus Brown Benjamin J Callahan Andrés Mauricio Caraballo-Rodríguez John Chase Emily K Cope Ricardo Da Silva Christian Diener Pieter C Dorrestein Gavin M Douglas Daniel M Durall Claire Duvallet Christian F Edwardson Madeleine Ernst Mehrbod Estaki Jennifer Fouquier Julia M Gauglitz Sean M Gibbons Deanna L Gibson Antonio Gonzalez Kestrel Gorlick Jiarong Guo Benjamin Hillmann Susan Holmes Hannes Holste Curtis Huttenhower Gavin A Huttley Stefan Janssen Alan K Jarmusch Lingjing Jiang Benjamin D Kaehler Kyo Bin Kang Christopher R Keefe Paul Keim Scott T Kelley Dan Knights Irina Koester Tomasz Kosciolek Jorden Kreps Morgan G I Langille Joslynn Lee Ruth Ley Yong-Xin Liu Erikka Loftfield Catherine Lozupone Massoud Maher Clarisse Marotz Bryan D Martin Daniel McDonald Lauren J McIver Alexey V Melnik Jessica L Metcalf Sydney C Morgan Jamie T Morton Ahmad Turan Naimey Jose A Navas-Molina Louis Felix Nothias Stephanie B Orchanian Talima Pearson Samuel L Peoples Daniel Petras Mary Lai Preuss Elmar Pruesse Lasse Buur Rasmussen Adam Rivers Michael S Robeson Patrick Rosenthal Nicola Segata Michael Shaffer Arron Shiffer Rashmi Sinha Se Jin Song John R Spear Austin D Swafford Luke R Thompson Pedro J Torres Pauline Trinh Anupriya Tripathi Peter J Turnbaugh Sabah Ul-Hasan Justin J J van der Hooft Fernando Vargas Yoshiki Vázquez-Baeza Emily Vogtmann Max von Hippel William Walters Yunhu Wan Mingxun Wang Jonathan Warren Kyle C Weber Charles H D Williamson Amy D Willis Zhenjiang Zech Xu Jesse R Zaneveld Yilong Zhang Qiyun Zhu Rob Knight J Gregory Caporaso

Nat Biotechnol 2019 Sep;37(9):1091

Center for Applied Microbiome Science, Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41587-019-0252-6DOI Listing
September 2019

Early E. casseliflavus gut colonization and outcomes of allogeneic hematopoietic cell transplantation.

PLoS One 2019 8;14(8):e0220850. Epub 2019 Aug 8.

Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States of America.

Gut dysbiosis has been associated with worse allogeneic hematopoietic cell transplantation (allo-HCT) outcomes. We reported an association between intrinsically vancomycin-resistant enterococci (iVRE: E. gallinarum and E. casseliflavus) gut colonization and lower post-transplant mortality. In this study, using an expanded cohort, we evaluated whether our previously observed association is species-specific. We included allo-HCT recipients with ≥1 positive rectal swab or stool culture for iVRE between days -14 and +14 of transplant. To investigate whether iVRE modulate the gut microbiota, we performed agar diffusion assays. To investigate whether iVRE differ in their ability to activate the aryl hydrocarbon receptor, we analyzed iVRE genomes for enzymes in the shikimate and tryptophan pathways. Sixty six (23 E. casseliflavus and 43 E. gallinarum) of the 908 allograft recipients (2011-2017) met our inclusion criteria. Overall survival was significantly higher in patients with E. casseliflavus (91% vs. 62% at 3 years, P = 0.04). In multivariable analysis, E. casseliflavus gut colonization was significantly associated with reduced all-cause mortality (hazard ratio 0.20, 95% confidence interval 0.04-0.91, P = 0.04). While agar assays were largely unremarkable, genome mining predicted that E. casseliflavus encodes a larger number of enzymes in the tryptophan metabolism pathway. In conclusion, E. casseliflavus gut colonization is associated with reduced post-HCT morality. Further research is needed to understand the mechanisms for this association.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220850PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687141PMC
March 2020

Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.

Authors:
Evan Bolyen Jai Ram Rideout Matthew R Dillon Nicholas A Bokulich Christian C Abnet Gabriel A Al-Ghalith Harriet Alexander Eric J Alm Manimozhiyan Arumugam Francesco Asnicar Yang Bai Jordan E Bisanz Kyle Bittinger Asker Brejnrod Colin J Brislawn C Titus Brown Benjamin J Callahan Andrés Mauricio Caraballo-Rodríguez John Chase Emily K Cope Ricardo Da Silva Christian Diener Pieter C Dorrestein Gavin M Douglas Daniel M Durall Claire Duvallet Christian F Edwardson Madeleine Ernst Mehrbod Estaki Jennifer Fouquier Julia M Gauglitz Sean M Gibbons Deanna L Gibson Antonio Gonzalez Kestrel Gorlick Jiarong Guo Benjamin Hillmann Susan Holmes Hannes Holste Curtis Huttenhower Gavin A Huttley Stefan Janssen Alan K Jarmusch Lingjing Jiang Benjamin D Kaehler Kyo Bin Kang Christopher R Keefe Paul Keim Scott T Kelley Dan Knights Irina Koester Tomasz Kosciolek Jorden Kreps Morgan G I Langille Joslynn Lee Ruth Ley Yong-Xin Liu Erikka Loftfield Catherine Lozupone Massoud Maher Clarisse Marotz Bryan D Martin Daniel McDonald Lauren J McIver Alexey V Melnik Jessica L Metcalf Sydney C Morgan Jamie T Morton Ahmad Turan Naimey Jose A Navas-Molina Louis Felix Nothias Stephanie B Orchanian Talima Pearson Samuel L Peoples Daniel Petras Mary Lai Preuss Elmar Pruesse Lasse Buur Rasmussen Adam Rivers Michael S Robeson Patrick Rosenthal Nicola Segata Michael Shaffer Arron Shiffer Rashmi Sinha Se Jin Song John R Spear Austin D Swafford Luke R Thompson Pedro J Torres Pauline Trinh Anupriya Tripathi Peter J Turnbaugh Sabah Ul-Hasan Justin J J van der Hooft Fernando Vargas Yoshiki Vázquez-Baeza Emily Vogtmann Max von Hippel William Walters Yunhu Wan Mingxun Wang Jonathan Warren Kyle C Weber Charles H D Williamson Amy D Willis Zhenjiang Zech Xu Jesse R Zaneveld Yilong Zhang Qiyun Zhu Rob Knight J Gregory Caporaso

Nat Biotechnol 2019 08;37(8):852-857

Center for Applied Microbiome Science, Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.

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http://dx.doi.org/10.1038/s41587-019-0209-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015180PMC
August 2019

Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans.

Cell Host Microbe 2019 06;25(6):789-802.e5

BioTechnology Institute, University of Minnesota, Saint Paul, MN 55108, USA; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.
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http://dx.doi.org/10.1016/j.chom.2019.05.005DOI Listing
June 2019

Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.

Nat Commun 2019 05 1;10(1):2012. Epub 2019 May 1.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55902, USA.

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.
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http://dx.doi.org/10.1038/s41467-019-09964-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494866PMC
May 2019

Microbiome Learning Repo (ML Repo): A public repository of microbiome regression and classification tasks.

Gigascience 2019 05;8(5)

Bioinformatics and Computational Biology, University of Minnesota, 200 Union Street SE, Minneapolis, MN 55455.

The use of machine learning in high-dimensional biological applications, such as the human microbiome, has grown exponentially in recent years, but algorithm developers often lack the domain expertise required for interpretation and curation of the heterogeneous microbiome datasets. We present Microbiome Learning Repo (ML Repo, available at https://knights-lab.github.io/MLRepo/), a public, web-based repository of 33 curated classification and regression tasks from 15 published human microbiome datasets. We highlight the use of ML Repo in several use cases to demonstrate its wide application, and we expect it to be an important resource for algorithm developers.
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http://dx.doi.org/10.1093/gigascience/giz042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493971PMC
May 2019

Bacterial community structure and function distinguish gut sites in captive red-shanked doucs (Pygathrix nemaeus).

Am J Primatol 2019 10 18;81(10-11):e22977. Epub 2019 Apr 18.

Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota.

The mammalian order primates contains wide species diversity. Members of the subfamily Colobinae are unique amongst extant primates in that their gastrointestinal systems more closely resemble those of ruminants than other members of the primate order. In the growing literature surrounding nonhuman primate microbiomes, analysis of microbial communities has been limited to the hindgut, since few studies have captured data on other gut sites, including the foregut of colobine primates. In this study, we used the red-shanked douc (Pygathrix nemaeus) as a model for colobine primates to study the relationship between gastrointestinal bacterial community structure and gut site within and between subjects. We analyzed fecal and pregastric stomach content samples, representative of the hindgut and foregut respectively, using 16S recombinant DNA (rDNA) sequencing and identified microbiota using closed-reference operational taxonomic unit (OTU) picking against the GreenGenes database. Our results show divergent bacterial communities clearly distinguish the foregut and hindgut microbiomes. We found higher bacterial biodiversity and a higher Firmicutes:Bacteroides ratio in the hindgut as opposed to the foregut. These gut sites showed strong associations with bacterial function. Specifically, energy metabolism was upregulated in the hindgut, whereas detoxification was increased in the foregut. Our results suggest a red-shanked douc's foregut microbiome is no more concordant with its own hindgut than it is with any other red-shanked douc's hindgut microbiome, thus reinforcing the notion that the bacterial communities of the foregut and hindgut are distinctly unique. OPEN PRACTICES: This article has been awarded Open Materials and Open Data badges. All materials and data are publicly accessible via the IRIS Repository at https://www.iris-database.org/iris/app/home/detail?id=york:934328. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
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http://dx.doi.org/10.1002/ajp.22977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800578PMC
October 2019

Genetic effects on the commensal microbiota in inflammatory bowel disease patients.

PLoS Genet 2019 03 8;15(3):e1008018. Epub 2019 Mar 8.

Department of Gastroenterology, Saint Antoine Hospital, Paris, France.

Several bacteria in the gut microbiota have been shown to be associated with inflammatory bowel disease (IBD), and dozens of IBD genetic variants have been identified in genome-wide association studies. However, the role of the microbiota in the etiology of IBD in terms of host genetic susceptibility remains unclear. Here, we studied the association between four major genetic variants associated with an increased risk of IBD and bacterial taxa in up to 633 IBD cases. We performed systematic screening for associations, identifying and replicating associations between NOD2 variants and two taxa: the Roseburia genus and the Faecalibacterium prausnitzii species. By exploring the overall association patterns between genes and bacteria, we found that IBD risk alleles were significantly enriched for associations concordant with bacteria-IBD associations. To understand the significance of this pattern in terms of the study design and known effects from the literature, we used counterfactual principles to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. Our analyses showed evidence that the disease risk of these genetic variants were likely to be partially mediated by the microbiome. We confirmed these results in extensive simulation studies and sensitivity analyses using the association between NOD2 and F. prausnitzii as a case study.
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http://dx.doi.org/10.1371/journal.pgen.1008018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426259PMC
March 2019

Characterization of Campylobacter jejuni, Campylobacter upsaliensis, and a novel Campylobacter sp. in a captive non-human primate zoological collection.

J Med Primatol 2019 04 9;48(2):114-122. Epub 2018 Dec 9.

Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts.

Background: The aim of this study was to longitudinally investigate the prevalence and characterization of Campylobacter spp. from non-human primates primate (NHP) with a history of endemic diarrhea housed at Como Park Zoo.

Methods: Fecal samples from 33 symptom-free NHP belonging to eight different species were collected weekly for 9 weeks. Species-level characterization and phylogenetic analysis of isolates included biochemical testing and 16S rRNA sequencing.

Results: Campylobacter spp. were isolated from the feces of 42% (14/33) of the primates. Three Campylobacter spp. (C upsaliensis, C jejuni, and novel Campylobacter sp.) were identified from three NHP species. A possible positive host Campylobacter species-specificity was observed. However, no statistical association was observed between the isolation of Campylobacter spp. and age and sex of the animal.

Conclusions: The study revealed the value of conducting repeated fecal sampling to establish the overall prevalence of Campylobacter in zoo-maintained NHP; it also importantly identifies a novel Campylobacter sp. isolated from white-faced saki monkeys.
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http://dx.doi.org/10.1111/jmp.12393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570501PMC
April 2019

Evaluating the Information Content of Shallow Shotgun Metagenomics.

mSystems 2018 Nov-Dec;3(6). Epub 2018 Nov 13.

Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, USA.

Although microbial communities are associated with human, environmental, plant, and animal health, there exists no cost-effective method for precisely characterizing species and genes in such communities. While deep whole-metagenome shotgun (WMS) sequencing provides high taxonomic and functional resolution, it is often prohibitively expensive for large-scale studies. The prevailing alternative, 16S rRNA gene amplicon (16S) sequencing, often does not resolve taxonomy past the genus level and provides only moderately accurate predictions of the functional profile; thus, there is currently no widely accepted approach to affordable, high-resolution, taxonomic, and functional microbiome analysis. To address this technology gap, we evaluated the information content of shallow shotgun sequencing with as low as 0.5 million sequences per sample as an alternative to 16S sequencing for large human microbiome studies. We describe a library preparation protocol enabling shallow shotgun sequencing at approximately the same per-sample cost as 16S sequencing. We analyzed multiple real and simulated biological data sets, including two novel human stool samples with ultradeep sequencing of 2.5 billion sequences per sample, and found that shallow shotgun sequencing recovers more-accurate species-level taxonomic and functional profiles of the human microbiome than 16S sequencing. We discuss the inherent limitations of shallow shotgun sequencing and note that 16S sequencing remains a valuable and important method for taxonomic profiling of novel environments. Although deep WMS sequencing remains the gold standard for high-resolution microbiome analysis, we recommend that researchers consider shallow shotgun sequencing as a useful alternative to 16S sequencing for large-scale human microbiome research studies where WMS sequencing may be cost-prohibitive. A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies.
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http://dx.doi.org/10.1128/mSystems.00069-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234283PMC
November 2018

US Immigration Westernizes the Human Gut Microbiome.

Cell 2018 11;175(4):962-972.e10

Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN 55455, USA; Biotechnology Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the United States is associated with immediate loss of gut microbiome diversity and function in which US-associated strains and functions displace native strains and functions. These effects increase with duration of US residence and are compounded by obesity and across generations.
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http://dx.doi.org/10.1016/j.cell.2018.10.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498444PMC
November 2018

Urinary microbiome associated with chronic allograft dysfunction in kidney transplant recipients.

Clin Transplant 2018 12 18;32(12):e13436. Epub 2018 Nov 18.

Department of Medicine, Nephrology Division, Hennepin Healthcare, Minneapolis, Minnesota.

Background: We performed a study to identify differences in the urinary microbiome associated with chronic allograft dysfunction (CAD) and compared the urinary microbiome of male and female transplant recipients with CAD.

Methods: This case-control study enrolled 67 patients within the Deterioration of Kidney Allograft Function (DeKAF) Genomics cohort at two transplant centers. CAD was defined as a greater than 25% rise in serum creatinine relative to a 3 month post-transplant baseline. Urine samples from patients with and without CAD were analyzed using 16S V4 bacterial ribosomal DNA sequences.

Results: Corynebacterium was more prevalent in female and male patients with CAD compared to non-CAD female patients (P = 0.0005). A total 21 distinct Operational Taxonomic Unit (OTUs) were identified as significantly different when comparing CAD and non-CAD patients using Kruskal-Wallis (P < 0.01). A subset analysis of female patients with CAD compared to non-CAD females identified similar differentially abundant OTUs, including the genera Corynebacterium and Staphylococcus (Kruskal-Wallis; P = 0.01; P = 0.004, respectively). Male CAD vs female CAD analysis showed greater abundance of phylum Proteobacteria in males.

Conclusion: There were differences in the urinary microbiome when comparing female and male CAD patients with their female non-CAD counterparts and these differences persisted in the subset analysis limited to female patients only.
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http://dx.doi.org/10.1111/ctr.13436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984979PMC
December 2018