Thomas Haggerty - Academia.edu (original) (raw)

Papers by Thomas Haggerty

The Californians Fighting Against Coronavirus Together Study (CA-FACTS), Placer County is a colla... more The Californians Fighting Against Coronavirus Together Study (CA-FACTS), Placer County is a collaboration between Stanford University and the County of Placer, begun in October 2020 and completed in April of 2021. Among a representative sample of county residents who both provided a blood spot for testing and completed a survey on demographics and behaviors, seroprevalence increased from 1.2% in January 2021 to 43.6% in March 2021, due in part to an increasing proportion of the population being vaccinated.

Nature Communications, 2022

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of con... more Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS...

This article cites 26 articles, 10 of which can be accessed free

Helicobacter pylori in cathartic stools of subjects with and without cimetidine-induced hypochlor... more Helicobacter pylori in cathartic stools of subjects with and without cimetidine-induced hypochlorhydria

Scientific Reports, 2020

The potential role of enteric viral infections and the developing infant virome in affecting immu... more The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log10 vs. 2.25 log10, p = 0.002), particularly from potential viral pathogens (2.78log10 vs. 0.83log10, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus sh...

Science of The Total Environment, 2021

Metabolic transformations play critical roles in the bioavailability and toxicities of environmen... more Metabolic transformations play critical roles in the bioavailability and toxicities of environmental pollutants and toxicants. However, most previous research has focused on the metabolic reactions in host tissues, the gut microbiota-mediated biotransformation of environmental compounds is understudied. Using triclocarban (TCC) as a model environmental compound, here we study the metabolic fate of TCC in gut tissues and determine the roles of gut microbiota involved. We find that compared with other tissues, the colon tissue has a unique metabolic profile of TCC, with high abundance of the parent compound TCC and its free-form metabolites. Using a variety of approaches including antibiotic-mediated suppression of gut bacteria in vivo, germ-free mice, and in vitro culture of fecal bacteria, we found that the unique metabolic profile of TCC in the colon is mediated by the actions of gut microbiota. Overall, our findings support that gut microbiota plays important roles in colonic metabolism of TCC, highlighting the importance to consider the contributions of gut microbiota in toxicology evaluation of environmental compounds.

EMBO molecular medicine, 2017

In 2016, the US Food and Drug Administration banned the use of specific microbicides in some hous... more In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the gut microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction or loss of microbial diversity of either infant or maternal gut microbiotas. Broadly an...

In 2016, the US Food and Drug Administration banned the use of specific microbicides in some hous... more In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products. This decision was due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the intestinal microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction of either infant or maternal intestinal microbiotas following...

Open Forum Infectious Diseases, 2014

Background. The human microbiome has been implicated in the development and maintenance of obesit... more Background. The human microbiome has been implicated in the development and maintenance of obesity. We hypothesized that triclosan and triclocarban(TCS), microbicides found in many household and personal care products (HPCP) and present in 75% of US human urine samples, play a role in altering microbiota, metabolic function and weight. Methods. In a double-blind, randomized, cross-over study participants were given TCS or non-TCS containing toothpaste, dish and hand soap for 4 months then switched arms. Of 16 subjects enrolled, 13 completed the trial. Blood, stool, skin swabs, gingival plaque, saliva, urine samples and weights were obtained at baselineand at regular intervals throughout each period. Bloods were analyzed for metabolic and endocrine markers and urines for TCS. Illumina sequencing of stool skin, skin, saliva and gingival plaque is underway. All statistics were performed in R. Results. In the TCS arm, TC levels where higher (median 25,555 pg/ul) than in the non-TCS arm (median 218 pg/ul) (p < 0.001). No significant differences were found in testosterone, T4 or TSH levels or in 17 adipocytokines on the obesity panel. Six subjects gained more than 0.6% of body weight (the highest quartile) in the TCS arm but lost or stayed at the same weight in the non-TCS arm; the reverse (weight gain in non-TCS but not in TCS arm) was seen in only one person (OR = 6, p = 0.13, McNemar test). Microbiota analysis of saliva, skin and stool samples is pending. Conclusion. In this pilot study we found that individuals were somewhat more likely to gain weight while using TCS-HPCP than when not using TCS-HPCP; this was not explained by hormonal or adipocytokine changes. Sequencing studies will examine whether TCS affects microbial communities. Disclosures. All authors: No reported disclosures.

mSphere, 2016

W e agree with Kennedy et al. (1) that "TCS" was used as an acronym that

The American Journal of Gastroenterology, 2007

Several large studies have shown a negative association between Helicobacter pylori (H. pylori) i... more Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux. METHODS: We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls). RESULTS: A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR = 0.18 [CI 0.04-0.78]). This inverse association was seen only in overweight subjects (BMI ≥ 25, P value for interaction = 0.09). The effects of H. pylori and ghrelin were independent. CONCLUSION: Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.

Virology Journal, 2009

Background Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not... more Background Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not found in approximately 30–50% of cases. Picornaviral genera such as enterovirus, kobuvirus, cosavirus, parechovirus, hepatovirus, teschovirus, and cardiovirus have all been found in human and animal diarrhea. Modern technologies, especially deep sequencing, allow rapid, high-throughput screening of clinical samples such as stool for new infectious agents associated with human disease. Results A pool of 141 pediatric gastroenteritis samples that were previously found to be negative for known diarrheal viruses was subjected to pyrosequencing. From a total of 937,935 sequence reads, a collection of 849 reads distantly related to Aichi virus were assembled and found to comprise 75% of a novel picornavirus genome. The complete genome was subsequently cloned and found to share 52.3% nucleotide pairwise identity and 38.9% amino acid identity to Aichi virus. The low level of sequence identity s...

Journal of Virology, 2010

Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Pico... more Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Picornaviridae family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate in vitro , hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike...

Proceedings of the National Academy of Sciences, 2008

Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but litt... more Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens [637 (89%) from patients with acute respiratory illness] and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic...

Plos One, 2011

Tauopathic pathways lead to degenerative changes in Alzheimer&amp;amp;amp;amp;#39;s disease a... more Tauopathic pathways lead to degenerative changes in Alzheimer&amp;amp;amp;amp;#39;s disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson&amp;amp;amp;amp;#39;s disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn) A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in

The Californians Fighting Against Coronavirus Together Study (CA-FACTS), Placer County is a colla... more The Californians Fighting Against Coronavirus Together Study (CA-FACTS), Placer County is a collaboration between Stanford University and the County of Placer, begun in October 2020 and completed in April of 2021. Among a representative sample of county residents who both provided a blood spot for testing and completed a survey on demographics and behaviors, seroprevalence increased from 1.2% in January 2021 to 43.6% in March 2021, due in part to an increasing proportion of the population being vaccinated.

Nature Communications, 2022

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of con... more Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS...

This article cites 26 articles, 10 of which can be accessed free

Helicobacter pylori in cathartic stools of subjects with and without cimetidine-induced hypochlor... more Helicobacter pylori in cathartic stools of subjects with and without cimetidine-induced hypochlorhydria

Scientific Reports, 2020

The potential role of enteric viral infections and the developing infant virome in affecting immu... more The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log10 vs. 2.25 log10, p = 0.002), particularly from potential viral pathogens (2.78log10 vs. 0.83log10, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus sh...

Science of The Total Environment, 2021

Metabolic transformations play critical roles in the bioavailability and toxicities of environmen... more Metabolic transformations play critical roles in the bioavailability and toxicities of environmental pollutants and toxicants. However, most previous research has focused on the metabolic reactions in host tissues, the gut microbiota-mediated biotransformation of environmental compounds is understudied. Using triclocarban (TCC) as a model environmental compound, here we study the metabolic fate of TCC in gut tissues and determine the roles of gut microbiota involved. We find that compared with other tissues, the colon tissue has a unique metabolic profile of TCC, with high abundance of the parent compound TCC and its free-form metabolites. Using a variety of approaches including antibiotic-mediated suppression of gut bacteria in vivo, germ-free mice, and in vitro culture of fecal bacteria, we found that the unique metabolic profile of TCC in the colon is mediated by the actions of gut microbiota. Overall, our findings support that gut microbiota plays important roles in colonic metabolism of TCC, highlighting the importance to consider the contributions of gut microbiota in toxicology evaluation of environmental compounds.

EMBO molecular medicine, 2017

In 2016, the US Food and Drug Administration banned the use of specific microbicides in some hous... more In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the gut microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction or loss of microbial diversity of either infant or maternal gut microbiotas. Broadly an...

In 2016, the US Food and Drug Administration banned the use of specific microbicides in some hous... more In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products. This decision was due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the intestinal microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction of either infant or maternal intestinal microbiotas following...

Open Forum Infectious Diseases, 2014

Background. The human microbiome has been implicated in the development and maintenance of obesit... more Background. The human microbiome has been implicated in the development and maintenance of obesity. We hypothesized that triclosan and triclocarban(TCS), microbicides found in many household and personal care products (HPCP) and present in 75% of US human urine samples, play a role in altering microbiota, metabolic function and weight. Methods. In a double-blind, randomized, cross-over study participants were given TCS or non-TCS containing toothpaste, dish and hand soap for 4 months then switched arms. Of 16 subjects enrolled, 13 completed the trial. Blood, stool, skin swabs, gingival plaque, saliva, urine samples and weights were obtained at baselineand at regular intervals throughout each period. Bloods were analyzed for metabolic and endocrine markers and urines for TCS. Illumina sequencing of stool skin, skin, saliva and gingival plaque is underway. All statistics were performed in R. Results. In the TCS arm, TC levels where higher (median 25,555 pg/ul) than in the non-TCS arm (median 218 pg/ul) (p < 0.001). No significant differences were found in testosterone, T4 or TSH levels or in 17 adipocytokines on the obesity panel. Six subjects gained more than 0.6% of body weight (the highest quartile) in the TCS arm but lost or stayed at the same weight in the non-TCS arm; the reverse (weight gain in non-TCS but not in TCS arm) was seen in only one person (OR = 6, p = 0.13, McNemar test). Microbiota analysis of saliva, skin and stool samples is pending. Conclusion. In this pilot study we found that individuals were somewhat more likely to gain weight while using TCS-HPCP than when not using TCS-HPCP; this was not explained by hormonal or adipocytokine changes. Sequencing studies will examine whether TCS affects microbial communities. Disclosures. All authors: No reported disclosures.

mSphere, 2016

W e agree with Kennedy et al. (1) that "TCS" was used as an acronym that

The American Journal of Gastroenterology, 2007

Several large studies have shown a negative association between Helicobacter pylori (H. pylori) i... more Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux. METHODS: We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls). RESULTS: A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR = 0.18 [CI 0.04-0.78]). This inverse association was seen only in overweight subjects (BMI ≥ 25, P value for interaction = 0.09). The effects of H. pylori and ghrelin were independent. CONCLUSION: Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.

Virology Journal, 2009

Background Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not... more Background Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not found in approximately 30–50% of cases. Picornaviral genera such as enterovirus, kobuvirus, cosavirus, parechovirus, hepatovirus, teschovirus, and cardiovirus have all been found in human and animal diarrhea. Modern technologies, especially deep sequencing, allow rapid, high-throughput screening of clinical samples such as stool for new infectious agents associated with human disease. Results A pool of 141 pediatric gastroenteritis samples that were previously found to be negative for known diarrheal viruses was subjected to pyrosequencing. From a total of 937,935 sequence reads, a collection of 849 reads distantly related to Aichi virus were assembled and found to comprise 75% of a novel picornavirus genome. The complete genome was subsequently cloned and found to share 52.3% nucleotide pairwise identity and 38.9% amino acid identity to Aichi virus. The low level of sequence identity s...

Journal of Virology, 2010

Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Pico... more Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Picornaviridae family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate in vitro , hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike...

Proceedings of the National Academy of Sciences, 2008

Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but litt... more Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens [637 (89%) from patients with acute respiratory illness] and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic...

Plos One, 2011

Tauopathic pathways lead to degenerative changes in Alzheimer&amp;amp;amp;amp;#39;s disease a... more Tauopathic pathways lead to degenerative changes in Alzheimer&amp;amp;amp;amp;#39;s disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson&amp;amp;amp;amp;#39;s disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn) A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in