Todd Z DeSantis

Second Genome · Department of Informatics

Objective Inflammatory bowel disease (IBD) is a heterogenous disease in which the microbiome has been shown to play an important role. However, the precise homeostatic or pathological functions played by bacteria remain unclear. Most published studies report taxa-disease associations based on single-technology analysis of a single cohort, potential...

While healthy gut microbiomes are critical to human health, pertinent microbial processes remain largely undefined, partially due to differential bias among profiling techniques. By simultaneously integrating multiple profiling methods, multi-omic analysis can define generalizable microbial processes, and is especially useful in understanding compl...

Malnutrition can influence maternal physiology and programme offspring development. Yet, in pregnancy, little is known about how dietary challenges that influence maternal phenotype affect gut structure and function. Emerging evidence suggests that interactions between the environment, multidrug resistance (MDR) transporters and microbes may influe...

While healthy gut microbiomes are critical to human health, pertinent microbial processes remain largely undefined, partially due to differential bias among profiling techniques. By simultaneously integrating multiple profiling methods, multi-omic analysis can define generalizable microbial pro-cesses, and is especially useful in understanding comp...

Immune-checkpoint inhibitor (ICI) therapy releases the molecular “brakes” on the immune system thereby promoting robust anti-tumor immune responses. However, many patients do not respond to ICI therapy due to development of primary and secondary resistance, and this population represents a large unmet medical need. The critical role of C-X-C motif...

Microbiome-driven drug discovery holds great promise for therapeutic development. However, identification of disease-associated microbiome-host interactions are challenging, owing largely to the complexity of a diverse community and the myriad of direct and indirect interactions through which the microbiome can influence its host. Moreover, inflamm...

Intestinal barrier dysfunction or the loss of the epithelial integrity allowing the permeation of microorganisms, dietary antigens and other particles into the gastrointestinal (GI) mucosa results in the activation of the immune system and drives inflammation during IBD. Ongoing inflammation in the GI tract and loss of the mucosal barrier are key f...

Background In Inflammatory Bowel Disease (IBD), intestinal barrier dysfunction and epithelial cell injury are believed to be associated with activation of the immune system to drive disease-associated inflammation, which together constitute key features of active disease. Existing drugs used to treat IBD induce endoscopic remission and improvements...

The gut microbiome is an important determinant for the success of anti-tumor therapies including chemotherapeutics and anti-checkpoint inhibitors. In this study we wanted to leverage Second Genome’s large and curated microbiome database coupled with its proprietary bioinformatics and machine learning tools to discover bioactive peptides from Bifido...

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder influenced by both genetic and environmental factors. Recently, gut dysbiosis has emerged as a powerful contributor to ASD symptoms. In this study, we recruited over 100 age-matched sibling pairs (between 2 and 8 years old) where one had an Autism ASD diagnosis and the other wa...

Malnutrition can influence maternal physiology and programme offspring development. Yet, in pregnancy, little is known about how dietary challenges that influence maternal phenotype affect gut structure and function. Emerging evidence suggests that interactions between the environment, multidrug resistance (MDR) transporters and microbes may influe...

Background: Sequencing partial 16S rRNA genes is a cost effective method for quantifying the microbial composition of an environment, such as the human gut. However, downstream analysis relies on binning reads into microbial groups by either considering each unique sequence as a different microbe, querying a database to get taxonomic labels from s...

Metabolomic analyses of human gut microbiome samples can unveil the metabolic potential of host tissues and the numerous microorganisms they support, concurrently. As such, metabolomic information bears immense potential to improve disease diagnosis and therapeutic drug discovery. Unfortunately, as cohort sizes increase, comprehensive metabolomic p...

The composition of the gut microbiota affects cancer development, progression, and response to therapy. A number of commensal bacteria, including Bifidobacterium, have been associated with increased response to immune checkpoint inhibitors in mouse tumor models, as well as in melanoma patients. We hypothesized that secreted peptides or proteins con...

The gut microbiota has emerged as an important player in cancer pathology, and increasing evidence supports its role in clinical response to immune checkpoint inhibitor (ICI) therapy. However, the specific microbiome-derived factors responsible for the improved response to ICI therapy remain unknown. Second Genome has developed a unique discovery p...

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn’s disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and with...

Following the publication of this article [1], the authors reported errors in Figs. 1, 2 and 5. Due to a typesetting error the asterisks denoting significance were missing from the published figures.

Abstract Background Shotgun metagenomic sequencing reveals the potential in microbial communities. However, lower-cost 16S ribosomal RNA (rRNA) gene sequencing provides taxonomic, not functional, observations. To remedy this, we previously introduced Piphillin, a software package that predicts functional metagenomic content based on the frequency o...

The microbiome shapes the metabolic and immunological landscape of individuals in health and disease and represents a new robust source of bioactive molecules with therapeutic potential. Second Genome’s large and curated microbiome database coupled with its proprietary bioinformatics and machine learning pipeline enables the discovery of novel micr...

p>The gut microbiome is a key contributor to the maintenance of host physiology. At the same time, increasing evidence implicates microbiome dysbiosis as a key determinant of numerous metabolic and inflammatory disorders. It is, therefore, of paramount importance to understand the interactions between the host and gut microbiota. Second Genome has...

The microbiome shapes the metabolic and immunological landscape of individuals in health and disease and represents a new robust source of bioactive molecules with therapeutic potential. Second Genome’s large and curated microbiome database coupled with its proprietary bioinformatics and machine learning pipeline enables the discovery of novel micr...

The composition of the gut microbiota affects cancer development, progression, and response to therapy. A number of commensal bacteria, including , have been associated with increased response to immune checkpoint inhibitors in mouse tumor models and in cancer patients. We hypothesized that secreted peptides or proteins are driving the -mediated ef...

Microbes colonizing colorectal cancer (CRC) tumors have the potential to affect disease, and vice-versa. The manner in which they differ from microbes in physically adjacent tissue or stool within the case in terms of both, taxonomy and biological activity remains unclear. In this study, we systematically analyzed previously published 16S rRNA sequ...

Principal Co-ordinates Analysis (PCoA) depicting the relationship between microbial composition from different tumor:tumor-adjacent study cohorts and their phenotypes. Plot points indicate individual samples, shapes indicate disease status (circle: Tumor, triangle: Tumor adjacent) and colors indicate various studies included in the meta-analysis (T...

Distribution of major phyla across the comparison groups tumor biopsy, tumor-adjacent biopsy and fecal samples included in the study. Tumor biopsy had the highest prevalence of Fusobacteria across samples while fecal samples had a high prevalence of Firmicutes while tumor-adjacent biopsy samples demonstrated an intermediated distribution for these...

Differentially abundant genera in CRC tumor biopsy as compared to tumor-adjacent biopsy identified by the Random Effects Model (REM). Taxonomy follows the convention of family, genus. Abbreviations for S2 Table: LogFC: Log2Fold Change, τ2: The (total) amount of heterogeneity among the true effects, SE: Standard error, QE: Test statistic for the tes...

Principal Co-ordinates Analysis (PCoA) depicting the relationship between microbial composition from paired tumor:fecal study cohorts and their phenotypes. Plot points indicate individual samples, shapes indicate disease status (circle: Biopsy, CRC: Colorectal cancer) and colors indicate various studies included in the meta-analysis (Target gene an...

Variable importance of different random forest classifiers. This figure depicts features ranked by their importance (Top 20 features depicted, most important at top to least at bottom) in the random forest classifier built to classify CRC tumor and tumor adjacent OR fecal samples. Each row is a microbial genera. (A) The microbial tumor:tumor-adjace...

Differentially abundant genera in CRC tumor biopsy as compared to fecal samples obtained from the same case identified by the random effects model (REM). Taxonomy follows the convention of family, genus. Abbreviations for S3 Table: LogFC: Log2Fold Change, τ2: The (total) amount of heterogeneity among the true effects, SE: Standard error, QE: Test s...

Genera present in both fecal and mucosal samples, only in fecal samples and only in biopsy samples. (DOCX)

Links to access raw data for cohorts included in the study. (DOCX)

Malnutrition is a global threat to pregnancy health and impacts offspring development. Establishing an optimal pregnancy environment requires the coordination of maternal metabolic and immune pathways, which converge at the gut. Diet, metabolic and immune dysfunctions have been associated with gut dysbiosis in the non-pregnant individual. In pregna...

Objective Colorectal cancer (CRC) is the second leading cause of cancer-associated mortality in the USA. The faecal microbiome may provide non-invasive biomarkers of CRC and indicate transition in the adenoma–carcinoma sequence. Re-analysing raw sequence and metadata from several studies uniformly, we sought to identify a composite and generalisabl...

Functional analysis of a clinical microbiome facilitates the elucidation of mechanisms by which microbiome perturbation can cause a phenotypic change in the patient. The direct approach for the analysis of the functional capacity of the microbiome is via shotgun metagenomics. An inexpensive method to estimate the functional capacity of a microbial...

16S rRNA gene amplicon sequences passing the identity threshold to the reference BioCyc genomes. Percentage of amplicon sequences from three datasets passing identity cutoffs from 0.75 to 1.00 to 16S rRNA gene sequences in BioCyc genome database were depicted. Solid line, human oral biopsy dataset; dotted line, rat feces dataset; dashed line, hyper...

DESeq2 to test differential abundance from Piphillin results. (DOCX)

Sensitivity and specificity in identifying differentially abundant BioCyc RXNs from Piphillin against corresponding shotgun metagenomics. (A) True positive rate and false positive rate of detecting significantly differentially abundant BioCyc RXNs in human oral biopsy sample. Numbers next to each point represents identity cutoff used for Piphillin....

BioCyc as a reference database for Piphillin. (DOCX)

Spearman’s correlation coefficient between BioCyc Piphillin results and shotgun metagenomics at ten different identity cutoff tested in Piphillin. Spearman’s correlation coefficient was calculated for each sample and mean, 1st and 3rd quartiles are depicted by the boxes. Whiskers extend to the furthest points within 150% of the interquartile range....

Dispersion plot showing the dispersion against the mean of normalized counts of human oral biopsy samples. (A) Metagenomics distribution. (B) KEGG Piphillin distribution. (C) PICRUSt distribution. (TIFF)

Whole-genome amplification (WGA) has become an important tool to explore the genomic information of microorganisms in an environmental sample with limited biomass, however potential selective biases during the amplification processes are poorly understood. Here, we describe the effects of WGA on 31 different microbial communities from five biotopes...

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without r...

Molecular techniques have uncovered vast numbers of organisms in the cystic fibrosis (CF) airways, the clinical significance of which is yet to be determined. The aim of this study was to describe and compare the microbial communities of the lower airway of clinically stable children with CF and children without CF. Bronchoalveolar lavage (BAL) flu...

Coral disease is one of the major causes of reef degradation. Dark Spot Syndrome (DSS) was described in the early 1990's as brown or purple amorphous areas of tissue on a coral and has since become one of the most prevalent diseases reported on Caribbean reefs. It has been identified in a number of coral species, but there is debate as to whether i...

Deciphering microbial communities and their role in Earth’s biosphere is crucial for addressing challenges in human health, agriculture, bioremediation and other natural processes. While next-generation sequencing platforms are still under development to improve accuracy, read length and sequencing depth, microarray-based methods have become an att...

Clostridium difficile infections (CDI) are caused by colonization and growth of toxigenic strains of C. difficile in individuals whose intestinal microbiota has been perturbed, in most cases following antimicrobial therapy. Determination of the protective commensal gut community members could inform the development of treatments for CDI. Here, we u...

Earth harbors an enormous portion of subsurface microbial life, whose microbiome flux across geographical locations remains mainly unexplored due to difficult access to samples. Here, we investigated the microbiome relatedness of subsurface biofilms of two sulfidic springs in southeast Germany that have similar physical and chemical parameters and...

Coral diseases impact reefs globally. Although we continue to describe diseases, little is known about the etiology or progression of even the most common cases. To examine a spectrum of coral health and determine factors of disease progression we examined Orbicella faveolata exhibiting signs of Yellow Band Disease (YBD), a widespread condition in...

Background: Intestinal microbiome constitutes a symbiotic ecosystem that is essential for health, and changes in its composition/function cause various illnesses. Biochemical milieu shapes the structure and function of the microbiome. Recently, we found marked differences in the abundance of numerous bacterial taxa between ESRD and healthy individ...

Wastewater treatment plants use a variety of bioreactor types and configurations to remove organic matter and nutrients. Little is known regarding the effects of different configurations and within-plant immigration on microbial community dynamics. Previously, we found that the structure of ammonia-oxidizing bacterial (AOB) communities in a full-sc...

Coral disease is a global problem. Diseases are typically named or described based on macroscopic changes, but broad signs of coral distress such as tissue loss or discoloration are unlikely to be specific to a particular pathogen. For example, there appear to be multiple diseases that manifest the rapid tissue loss that characterizes ‘white plague...

Tibetan lakes represent a unique microbial environment and are a good ecosystem to investigate the microbial diversity of high mountain lakes and their relationship with environmental factors. The diversity and community structure of bacterioplankton in Tibetan lakes was determined using DNA fingerprinting analysis, high-density 16S rRNA gene micro...

Background The development of Tuber melanosporum mycorrhizal symbiosis is associated with the production of an area devoid of vegetation (commonly referred to by the French word ‘brûlé’) around the symbiotic plants and where the fruiting bodies of T. melanosporum are usually collected. The extent of the ecological impact of such an area is still be...

Heatmap of the OTUs that were both significantly different and had nearly a 2-fold difference in average intensity between inside and outside the brûlé for Riemerella. In_1, In_2, In_3 and Out_1, Out_2, Out_3, respectively, were pools from inside and outside the brûlé and were used as replicate samples. (PDF)

Heatmap of the OTUs that were both significantly different and had nearly a 2-fold difference in average intensity between inside and outside the brûlé for Chryseobacterium. In_1, In_2, In_3 and Out_1, Out_2, Out_3, respectively, were pools from inside and outside the brûlé and were used as replicate samples. (PDF)

Heatmap of the OTUs that were both significantly different and had nearly a 2-fold difference in average intensity between inside and outside the brûlé for Flavobacterium. In_1, In_2, In_3 and Out_1, Out_2, Out_3, respectively, were pools from inside and outside the brûlé and were used as replicate samples. (EPS)

Heatmap of the OTUs that were both significantly different and had nearly a 2-fold difference in average intensity between inside and outside the brûlé for Pseudomonas. In_1, In_2, In_3 and Out_1, Out_2, Out_3, respectively, were pools from inside and outside the brûlé and were used as replicate samples. (EPS)

Details of each considered truffle-ground and soil chemical parameters for inside (IN) and outside (OUT) the four brûlés sampled. (DOC)

Heatmap of the OTUs that were both significantly different and had nearly a 2-fold difference in average intensity between inside and outside the brûlé for Pedobacter. In_1, In_2, In_3 and Out_1, Out_2, Out_3, respectively, were pools from inside and outside the brûlé and were used as replicate samples. (PDF)

Heatmap of the OTUs that were both significantly different and had nearly a 2-fold difference in average intensity between inside and outside the brûlé for Bacillus. In_1, In_2, In_3 and Out_1, Out_2, Out_3, respectively, were pools from inside and outside the brûlé and were used as replicate samples. (EPS)

Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown. Methods: Food allergy–prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) and wild-type (WT) control animals were subjected to oral sensitization with chicken egg ovalbumi...