Dan Knights

University of Colorado Boulder | CUB · Department of Computer Science (CS)

Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoin...

Introduction Early life gut microbiomes are important for brain and immune system development in animal models. Probiotic use has been proposed as a strategy to promote health via modulation of microbiomes. In this observational study, we explore if early life exposure to probiotics via the mother during pregnancy and lactation, is associated with...

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the...

Objective: The Low Biologically Available Glucose (LoBAG) diet was designed to improve glycemic control of type 2 diabetes mellitus (T2D). We evaluate changes in the gut microbiome when participants with T2D are given the LoBAG diet. Methods: Thirty-six participants with T2D taking metformin or no glucose-lowering medication were enrolled in a 12-w...

The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as the sole source of nutrition for the human infant, little is known about how variation in milk composition, and especially the milk microbiome, shapes the microbial communities in the infant gut. Here, we quantifie...

Motivation Differentiating ecosystems poses a complex, high-dimensional problem constrained by capturing relevant variation across species profiles. Researchers use pairwise distances and subsequent dimensionality reduction to highlight variation in a few dimensions. Despite popularity in analysis of ecological data, these low-dimensional visualiza...

Immigration to a highly industrialized nation has been associated with metabolic disease and simultaneous shifts in microbiota composition, but the underlying mechanisms are challenging to test in human studies. Here, we conducted a pilot study to assess the differential effects of human gut microbiota collected from the United States (US) and rura...

We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut mic...

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the...

Objectives: Dietary fibers (DF) elicit clinical benefits, but with significant inter-individual variation. It is unknown if DF strategies can be improved through personalization based on an individual’s gut microbiome. Our objective was to compare the immunometabolic effects of high doses of physicochemically- distinct DFs in adults with excess bod...

The microbiome is known to play a role in many human diseases, but identifying key microbes and their functions generally requires large studies due to the vast number of species and genes, and the high levels of intra-individual and inter-individual variation. 16S amplicon sequencing of the rRNA gene is commonly used for large studies due to its c...

Background Hmong men in Minnesota exhibit a high prevalence of gout and hyperuricemia. Although evidence of vitamin C’s effectiveness as a treatment for gout is mixed, analysis of therapeutic benefit based on an individual’s multiomic signature may identify predictive markers of treatment success. Objectives The primary objective of the Hmong Micr...

Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expr...

Wood decomposer fungi are grouped by how they extract sugars from lignocellulose. Brown rot fungi selectively degrade cellulose and hemicellulose, leaving lignin intact, and white rot fungi degrade all components. Many trees are susceptible to both rot types, giving carbon in Earth’s woody biomass, specifically lignin, a flexible fate that is affec...

The composition and function of early life gut bacterial communities (microbiomes) have been proposed to modulate health for the long term. In addition to bacteria, fungi (mycobiomes) also colonize the early life gut and have been implicated in health disorders such as asthma and obesity. Despite the potential importance of mycobiomes in health, th...

Vast numbers of microorganisms inhabit the mammalian gastrointestinal tract in a complex community referred to as the gut microbiome. An individual’s microbiome may be impacted by genetics, diet, and various environmental factors, and has been associated with many health states and diseases, though specific explanations are lacking. While these com...

Objectives Time-restricted eating (TRE) is a novel approach to obesity treatment that recently received attention. Very limited data exist regarding gut microbiome changes during TRE interventions in humans. Our objective was to characterize the gut microbiome of human participants before and after a 12-week TRE intervention. Methods In a randomiz...

While gut microbiome and host gene regulation independently contribute to gastrointestinal disorders, it is unclear how the two may interact to influence host pathophysiology. Here we developed a machine learning-based framework to jointly analyse paired host transcriptomic (n = 208) and gut microbiome (n = 208) profiles from colonic mucosal sample...

Background: Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25–35 kg/m2) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day)...

Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bi...

Background Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced...

In this brief report, we share lessons learned from the Immigrant Microbiome Project (IMP), a microbiome research study conducted in partnership with the Hmong and Karen communities in Minnesota. Members of the IMP academic-community research team and community advisory board reflected on the community-based participatory research (CBPR) approach u...

Background Intestinal microbiome disruption is a risk factor for poor outcomes after allogeneic hematopoietic cell transplantation (allo-HCT), but the factors that contribute to microbiome injury are not well understood. We hypothesized that nutrition contributes to microbiome composition during allo-HCT. Methods Along with 16S profiling of collect...

The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studie...

The recent incorporation of bacterial whole-genome sequencing (WGS) into Public Health laboratories has enhanced foodborne outbreak detection and source attribution. As a result, large volumes of publicly available datasets can be used to study the biology of foodborne pathogen populations at an unprecedented scale. To demonstrate the application o...

Methods for COVID-19 detection are necessary for public health efforts to monitor the spread of disease. Nasopharyngeal samples have been considered the best approach for COVID-19 testing.

Background and aims The gut virome includes eukaryotic viruses and bacteriophages that can shape the gut bacterial community and elicit host responses. The virome may be implicated in diseases such as irritable bowel syndrome (IBS), where gut bacteria play an important role in pathogenesis. Herein we provide a comprehensive and longitudinal charact...

Objectives Health outcomes in previous fiber intervention studies have been variable, potentially due to differences in gut microbiome composition. This study aimed to determine if the effect of fiber intervention on the microbiome differs by initial microbiome or the quantity of fiber provided. Methods This study was designed as a randomized, un-...

While the gut microbiome and host gene regulation separately contribute to gastrointestinal disorders, it is unclear how the two may interact to influence host pathophysiology. Here, we developed a machine learning-based framework to jointly analyze host transcriptomic and microbiome profiles from 416 colonic mucosal samples of patients with colore...

Background Although nasopharyngeal (NP) samples have been considered the gold standard for COVID-19 testing, variability in viral load across different anatomical sites could theoretically cause NP samples to be less sensitive than saliva or nasal samples in certain cases. Self-collected samples also have logistical advantages over NP samples, maki...

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)....

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)....

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...

p>(Cell 182, 1460–1473.e1–e17; September 17, 2020) In preparing the final version of this article, we overlooked some errors and we apologize for these shortcomings. None of these errors involved our data analyses or affected the conclusions presented in the manuscript. These errors have now been corrected online. 1. In Figure 2B the y axis should...

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 fo...

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 im...

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 dat...

One of the fundamental tasks in analyzing next-generation sequencing data is genome database search, in which DNA sequences are compared to known reference genomes for identification or annotation. Although algorithms exist for optimal database search with perfect sensitivity and specificity, these have largely been abandoned for next-generation se...

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 i...

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 weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1)heal...

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 p...

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 l...

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 thre...

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 fol...

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 i...

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a viable treatment option for many cancers but its clinical utility is limited due to the occurrence of graft-versus-host disease (GVHD). Understanding the impact of obesity on immune function has become increasingly important in the setting of the current obesity pandemic. We r...

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 two independent ethnic groups relocating from Thailand to the United States.

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...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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 wheth...

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...

Objectives: Previous studies have defined dietary patterns for comparison with microbiome features using factor analysis from food frequency questionnaires. In this study, we applied a new tree-based method to directly define dietary patterns from 24-hour food records. We aimed to determine if these patterns corresponded with microbial features....

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:/...

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 p...

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 communi...