Browsing by Subject "microbiome"

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The Complex Eco-Epidemiology of Tick Borne Disease: Ticks, Hosts and Pathobiomes in an Urbanizing Environment
(2017-08) Bennett, Steve
Emerging infectious diseases have become a rapidly increasing public health threat over the past 4 decades with the majority of pathogens being zoonotic or vector borne. Ticks are the second most important vector of disease globally, behind mosquitoes, and transmit a more diverse group of pathogens of medical importance than any other vector. Tick-borne diseases (TBDs) represent the most common vector-borne disease threats in North America, impacting both human and animal health. In Minnesota, the Lyme disease agent, Borrelia burgdorferi, emerged in 1980 and over the past two decades, incidence has risen over 700%. In order to better understand the local eco-epidemiology of these pathogens in the Twin Cities metro area a holistic approach to their ecology must be taken into account. The pathobiome concept has been introduced to ecological research to move beyond the ‘one pathogen= one disease’ principle. Pathogens must be evaluated within the framework of the microbial communities in which they exists. The impact of these communities can significantly drive disease transmission and vector competence. There are many gaps in data that currently exist in regards to the Ixodes scapularis pathobiome. To fill existing knowledge gaps, data were collected from the Metropolitan Mosquito Control District which had been trapping rodents and collecting ticks in the metro area since 1991. First, the pathobiome of Ixodes scapularis ticks was described. The analysis revealed significant changes depending upon the year ticks were collected. Next, tick and mammal population changes from 1993-2013 were analyzed to determine host vector relationships as well as vector range expansion. Ixodes scapularis have greatly expanded their range around the twin cities; however, urban development may have impacted that expansion. Additionally, the role of the Eastern chipmunk was shown to be important in local TBD ecology, and there is evidence of possible competition between tick species. Lastly, the impact of host blood meal and pathogen acquisition on the pathobiome of I. scapularis was examined. Both pathogens and host meal had a significant impact on tick pathobiome. The results from these studies are a step towards better understanding tick and TBD ecology and hopefully predicting and mitigating future transmission risk.
A consistent and predictable commercial broiler chicken bacterial microbiome in antibiotic-free production displays strong correlations with performance
(2018-01-16) Johnson, Timothy J; Youmans, Bonnie P; Noll, Sally; Cardona, Carol; Evans, Nicholas; Kernezos, Peter; Ngunjiri, John; Abundo, Michael; Lee, Chang-Won; tjj@umn.edu; Johnson, Timothy J
Defining the baseline bacterial microbiome is critical towards understanding its relationship with health and disease. In broiler chickens, numerous studies have aimed at defining the core microbiome, yet the core and its possible relationships with health and disease have been difficult to define due to lack of study power. Here, the most comprehensive microbiome-based effort to date in commercial broilers was undertaken. The primary goals of this study included understanding what constitutes core in the broiler gastrointestinal, respiratory, and barn environments; how these core players change across age, geography, and time; and which bacterial taxa correlate with enhanced bird performance in antibiotic-free flocks. Using 2,309 samples from 37 different commercial flocks within a vertically integrated broiler system, and metadata from 549 flocks within that system, the baseline bacterial microbiome was defined. The effects of age, sample type, flock, and successive flock cycles were compared, and results indicate a consistent, predictable, age-dependent bacterial microbiome, irrespective of flock. The tracheal bacterial microbiome of broilers was comprehensively defined for the first time, and interestingly, Lactobacillus was the dominant bacterial taxa in the trachea. Numerous bacterial taxa were identified which were strongly correlated with broiler chicken performance, across multiple tissues. While many positively correlated taxa were identified representing targets for future probiotic development, many negatively associated potential pathogens were identified in the absence of clinical disease, indicating subclinical dynamics occurring that impact performance. Overall, this work provides necessary baseline data for the development of effective antibiotic alternatives for sustainable poultry production.
Data from "Diverse Bacterial Communities Exist on Canine Skin and are Impacted by Cohabitation and Time"
(2016-11-17) Johnson, Timothy; Torres, Sheila; Danzeisen, Jessica; Clayton, Jonathan; Ward, Tonya; Knights, Dan; Huang, Hu; joh04207@umn.edu; Johnson, Timothy
This related study sampled 40 dogs from 20 households over the course of three seasons. Three skin sites were examined. The goal of the study was to determine if a core skin microbiome exists in dogs across time and body site, and if cohabitation impacts sharing of the skin microbiome. This dataset is a part of the Torres_Johnson Canine Microbiome Study.
Disruption of Gut Homeostasis by Opioids in the Early Stages of HIV Infection
(2014-12) Sindberg, Gregory
Opioids are a common comorbidity with HIV, with the use of opioids being present in up to 40% of the HIV infected population in some countries. Opioids have been shown to worsen HIV pathogenesis, including increased viral replication and faster progression to AIDS. HIV pathogenesis has been shown to be important in the gastrointestinal tract, where early loss of CD4+ T-cells has been observed in SIV infection and infection with either HIV or SIV show evidence of systemic bacterial translocation which is believed to drive HIV replication. Opioids are believed to worsen this effect and have been shown to increase bacterial translocation in HIV patients. The second chapter study was performed to understand the underlying disruption of gut homeostasis that contributes to bacterial translocation. HIV models were validated to show bacterial translocation, and then look at gut morphology, tight junction localization on gut epithelium, and immune function within the gut at early time points of exposure to HIV infection. Overall, based on the measures examined, opioids enhanced the pathogenesis of HIV in the gut at early infection which likely contributes to the greater replication and faster development of AIDS. While the loss of gut homeostasis is strongly believed to occur at least in part through changes in the host defenses in the gut, namely on immune populations and epithelial barrier integrity, recent evidence suggests that the microbiome of late stage HIV infected individuals is altered and may contribute to the observed disruption. The third chapter investigated the microbiome in early HIV infection to see if dysbiosis occurs, and whether opioids are associated with earlier changes. Using two animals models of infectious HIV, microbial dysbiosis was not observed at early time points of infection in either model. However, this study shows for the first time that morphine induced strong changes in the microbiome, which likely occurs via a combination of constipation and immune mediated effects. Altogether, these findings suggests another mechanism for morphine influencing HIV pathogenesis at early stages of disease. Combined, these studies show the wide ranging effects that opioids and HIV have on gut defenses, including epithelial barrier, immune function, and dysbiosis from the normal microbiome. While mostly descriptive in nature, the results give potential therapeutic opportunities, including potential oral administration of TLR2 and TLR4 antagonists, opioid antagonist naloxone, and bile acids in order to supplement deficiencies in metabolites observed.
The Effect of Abiotic and Biotic Factors, Symbiont Exchange Between Host Species, and Host Migration on Fungal Symbiont Community Composition and Diversity
(2021-10) Watson, Monica
Microbiomes, the ubiquitous communities of microbial symbionts residing within hosts, play important roles in host health, development, and fitness. While recent research has characterized the microbiomes of many different host species, our understanding of how environmental factors affect microbial community dynamics is still in nascent stages. In this dissertation, I investigate how biotic and abiotic environmental factors affect the diversity and composition of microbial symbiont communities within different host species. In chapter 1, I use a full factorial experimental plot design and culture-based methods to examine the effects of nutrient addition, large animal herbivore exclusion, and host tissue specificity on the fungal symbiont communities, known as endophytes, residing within the grass species Andropogon gerardii. While neither nutrient addition nor herbivore exclusion alone significantly affect the diversity or composition of culturable endophytes, in combination, nutrient addition and herbivore exclusion were associated with greater fungal symbiont diversity than found in other treatments. Further, while different host tissues harbored distinct fungal communities, diversity was greater in all plant host tissues sampled from plots with both nutrient addition and herbivore exclusion treatments. In chapter 2, using field collections and both culture- and sequence-based methods I compare fungal diversity and community composition in a migratory agricultural pest insect, Spodoptera frugiperda, its plant host, Sorghum bicolor, and soil collected beneath infested host plants. Finding fungal communities in insects were much more variable compared to fungal communities in plants and soil, I estimated contributions of these differing sources of fungal symbionts to the insect microbiome. Surprisingly, I find that insect fungal communities were more commonly attributed to other insect sources than to the plants on which they were feeding or to soil sources. In chapter 3, I examine the fungal symbiont communities in an overwintering population of S. frugiperda to the fungal symbiont of a migratory population to ask whether fungal symbiont communities differ over the course of migration. Specifically, I ask if the prevalence and abundance of entomopathogenic taxa is different in overwintering and migratory populations. In an analysis of environmental sources of insect fungal symbionts, I examined the fungal symbiont communities of plant hosts on which they feed at the overwintering and migratory sites. Fungal communities were surprisingly similar over the course of migration in insect hosts. While most fungal entomopathogens occurred in similar prevalence and abundance, there were two OTUs that were significantly different in abundance in the two states with one more abundant in overwintering populations and one more abundant in migratory populations. There was little evidence of fungal symbiont exchange between insects and plants. Together, these chapters characterize how both abiotic and biotic environmental factors affect fungal symbiont communities in plants and insects, the extent to which fungal symbionts may transmit among different hosts and ecological compartments, and how migration impacts microbial symbiont communities. This work has important implications for our understanding of the factors affecting microbial symbiont community dispersal and our ability to predict the effect of the environment on microbial symbiont communities in agriculturally significant species.
The effects of different feed additives on bird performance and the gastrointestinal microbiome of Salmonella-challenged broilers
(2018-01-16) Johnson, Timothy J; Evans, Nicholas; Karnezos, Peter; Sims, Michael; Youmans, Bonnie P; tjj@umn.edu; Johnson, Timothy J
A 42-day, 60-unit floor pen (10 pens per treatment, 25 birds per pen) Salmonella challenge study was conducted to determine the effects of supplementing broiler diets with virginiamycin (VM); medium chain fatty acids (MCFA); MCFA plus lactic acid (MCFA+LA) and a phytogenic blend (PB). Effects were assessed on bird performance and ileal, cecal, and litter microbiomes in birds challenged with Salmonella Typhimurium. Treatments were compared with a non-inoculated control group (NIC) and a Salmonella-challenged group without feed additives (IC). At days 14, 28, and 42 of age, all bird weights and intake were measured, 20 birds from each treatment were euthanized, and the ceca and ilea of euthanized birds were collected along with grab litter samples from each pen. Bacterial profiling was performed using 16S rRNA amplicon sequencing. Subsequent analyses were performed for measurements of alpha and beta bacterial community diversity, taxonomic classifications, and assessments of bacterial taxa that were shifted as a result of different treatments. At 42 days, body weights and mortality adjusted feed conversions for the UIC were significantly better (P<0.1) than the IC and VM while the MCFA, MCFA+LA and PB treatments were similar to the negative UIC. The Salmonella challenge itself had significant (P<0.01) effects on the bacterial microbiome of all sample types, with the greatest effects observed in the cecal microbiome of the bird. The VM treatment counteracted the effects of the Salmonella challenge on the overall bacterial communities of all sample types (P<0.05). While none of the antibiotic alternative treatments had significant effects on overall bacterial community structure consistent over time, specific bacterial taxa were impacted by several treatments. These included Candidatus Arthromitus (segmented filamentous bacteria), Peptostreptococcus, and Clostridium species. Unique signature taxonomic effects were identified for each treatment type, demonstrating attributes of each feed additive type in contributing to unique effects on the bird microbiota. Overall, this work identifies microbiome modulations conferred by different antibiotic alternatives under a Salmonella challenge.
The Effects of Green Tea Catechins on Oxidative Stress and Red Wheat on Measures of Oxidative and Nitrosative Stress, Colon Cancer Risk, and Gut Microbiome Composition
(2021-09) Fiecke, Chelsey
There have been very few long-term investigations of the in vivo antioxidant effects associated with consumption of green tea catechins, especially in healthy populations. In the first study, we evaluated the in vivo antioxidant effects of 12-month green tea catechin supplementation in healthy, postmenopausal women by measuring urinary excretion of secondary lipid peroxidation products. Green tea catechin supplementation reduced excretion of a nonpolar aldehyde that was identified as nonanal and/or decatrienal. Our results suggest that green tea catechins may exert modest antioxidant effects in healthy populations that do not have elevated oxidative stress.We previously reported that red wheat, the class of wheat used to make yeast bread products, reduced various colon cancer biomarkers. In the second study, we evaluated the chemopreventive effects of red wheat and the aleurone and testa layers by examining morphological markers of colon cancer risk (aberrant crypt foci; ACF), a cancer stem cell marker (doublecortin-like kinase 1; Dclk1), a marker of oxidative and nitrosative stress (3-nitrotyrosine; 3-NT), and gut microbiome composition. The number of medium ACF (3-5 aberrant crypts/ACF) was reduced by consumption of refined red wheat and the aleurone layer. Large ACF (≥ 6 aberrant crypts/ACF) were decreased by the whole and refined red wheat and refined white wheat. Refined red wheat and the aleurone and testa layers reduced 3-NT positivity in aberrant crypts. The microbiome composition differed between diet groups and was driven by altered abundances of Faecalitalea, Lactobacillus, Mucispirillum, and Phascolarctobacterium. Consumption of whole and refined red wheat resulted in enrichment of Faecalitalea and Lactobacillus and depletion of Mucispirillum. These results suggest that the aleurone and testa layers may be partially responsible for the chemoprevention by red wheat, which possibly involves reductions in oxidative/nitrosative stress and modulation of the gut microbiome. In summary, green tea catechins may exert modest antioxidant effects, even under physiological conditions of little oxidative stress. The aleurone and testa layers may play a role in chemoprevention by red wheat, which involves a reduction in oxidative/nitrosative stress and beneficial modulation of gut microbiome composition.
The effects of propolis on the honey bee (Apis mellifera) immune system and mouthpart microbiome
(2020-11) Dalenberg, Hollie
Honey bees (Apis mellifera) collect and apply antimicrobial plant resins to the interior of their nest cavity to form a lining called a propolis envelope. Previous studies show that exposure to a propolis envelope within the nest cavity resulted in reduced immune system activation in adult bees, however the mechanism for this reduction remained unclear. In Chapter 1, I tested the hypothesis that propolis exposure would reduce the general bacterial load (16S rRNA transcription) in and on honey bees, thereby reducing antimicrobial peptide (hymenoptaecin gene) expression by the honey bee innate immune system. The results showed that bees exposed to a propolis envelope in field colonies had significantly lower transcript levels of hymenoptaecin, but in contrast to previous studies had significantly greater 16S rRNA transcription, compared to bees in colonies without a propolis envelope. Bees held in cages had significantly greater hymenoptaecin expression and significantly greater 16S rRNA transcription compared to bees from colonies, suggesting that bees are exposed to different bacterial communities between colonies and cages. The consistent reduction in immune activation yet variable general bacterial loads upon propolis exposure, as seen in previous studies, suggests that there may be a relationship between propolis exposure and the abundance and diversity of specific bacterial species in particular microbial niches in and on the honey bee body. In Chapter 2, I hypothesized that the antimicrobial activity of a propolis envelope in bees from field colonies would influence the bacterial diversity and abundance of the worker mouthpart microbiome. The results of DNA sequencing revealed that the mouthparts of worker bees in colonies with a propolis envelope had significantly lower bacterial diversity and significantly higher bacterial abundance, compared to the mouthparts of bees in colonies without a propolis envelope. Based on the taxonomic results, the propolis envelope appeared to reduce pathogenic or opportunistic bacteria and to promote the proliferation of putatively beneficial bacteria on the honey bee mouthparts, thus reinforcing the core microbiome of the mouthpart niche. This work suggests that the mechanism for reduced immune system activation may be due to the antimicrobial properties of propolis reducing pathogenic and opportunistic bacterial species and promoting beneficial bacterial species in the mouthparts, which may affect disease transmission throughout the colony, thus promoting colony health and wellbeing. This relationships among honey bees, propolis, and microbes likely stems from their long evolutionary history together. The differences in bacterial loads between bees from field colonies and cages suggest that the antimicrobial properties of propolis, the community of microbes, and the individual immune response may vary according to the nest environment, availability of floral resources, and social and organizational behaviors of the bees within the colony.
Evaluating Microbial Community Interactions, using Ecology and Flux Balance Analysis
(2018-09) Seto, Charlie
This work is motivated by an interest in microbial interactions and their role in human health. I wanted to answer the question of how associations between therapeutic interventions and pathology intersected with the gut microbiome; I explore this in the association between proton pump inhibitor (PPI) usage and C. difficile infection (CDI) by assessing changes in the gut microbiome during PPI treatment in Chapter 1 of my thesis. I found that observed species diversity decreased while on PPI, but that I was unable to establish a mechanistic or metabolic framework from this data in line with previously published in vitro studies on C. difficile. I explore COnstraint Based Reconstruction and Analysis (COBRA) techniques to transform a taxonomic call (“Bifidobacterium longum”) into a whole-genome metabolic model and explore the limitations of the technique using custom constraints in Chapter 2 of my thesis. I find that the absence of custom constraints can create growth tradeoffs to fulfill a systems level objective of increasing biomass, but aggressively constraining a system towards a single point of balanced growth is not experimentally validated. After satisfying my understanding of the limitations of COBRA, I explore implementation of a sum of metabolic models pairwise framework, benchmarking a biomass only ab initio framework and a rate-of-change framework that requires a starting relative abundance. I benchmark this against existing framework MICOM and conclude that our framework does not predict for overly stable communities, especially at long timepoints into the future, making our framework a poor replacement for time-longitudinal prediction. In Chapter 4, I seek to answer the question of how to improve predictions such as those from Chapter 3; noticing that macromolecular degradation was not well implemented I implement granular macromolecular degradation but see no significant improvement in prediction accuracy. Lastly in Chapter 5, I take the pairwise community interaction framework established in Chapter 3 and ask if this framework can be used to predict probiotic candidates for host communities. I establish a framework that tests pairwise interactions of a probiotic with Host Community members and pathogens, then develop a scoring metric to identify organisms that integrate with host communities and exclude C. difficile. I explore my data for consistency with existing probiotic literature, finding Bifidobacterium strains that can competitively exclude C. difficile; I verify metabolic interactions by recapitulating a Low Risk/High Risk category from published literature, demonstrating that high risk microbiota indeed are more favorable to C. difficile engraftment, consistent with a publication-pending finding. I conclude by noting that microbe-microbe interactions can be described in ecological terms such as loss of diversity, but note that with community flux balance analysis, we can describe changes in diversity based on intermicrobial competition between pairs, which cumulatively results in ecologically relevant community rearrangement.
EVALUATION OF ASPERGILLUS ORYZAE POSTBIOTIC ON NUTRIENT DIGESTIBILITY, GUT MICROBIOME, AND METABOLOME IN GROWING PIGS FED HIGH FIBER DIETS
(2022-03) Zhu, Jinlong
Substantial amounts of low-cost, high fiber coproducts produced from various agro-industrial processes are incorporated into swine feed with the aim of reducing the cost and the environmental impacts of food animal production. Because dietary fiber (DF) is not well utilized by pigs, effective strategies are needed to improve the energy and nutrient utilization efficiency of using high fiber coproducts in swine diets. The objective of this thesis was to determine the potential of Aspergillus oryzae postbiotic (AOP) for improving nutrient digestibility of high fiber coproducts in growing pig diets and the underlying mechanisms. Results from the first and second experiments showed that the addition of 0.05% AOP to corn distillers dried grains with solubles, rice bran, or wheat middlings and diets containing these high fiber ingredients increased energy and nutrient digestibility in vivo and in vitro. The magnitude of the AOP response is ingredient- and diet-dependent, which suggested that the effectiveness of fiber-degrading feed additives is associated with DF type and composition of ingredients. Results from the third experiment suggested that dietary addition of AOP significantly altered the diversity and composition of the microbial community and metabolome in the ileal digesta and feces of growing pigs. Dietary addition of AOP alters the abundance of several bacteria that were significantly correlated with nutrient digestibility, including key players of the fiber-degrading bacteria. Overall, findings from this thesis provided the first evidence that AOP is effective in increasing the energy and nutritional value of swine diets containing different types of high fiber ingredients and new insights into mechanisms of action of AOP in pigs.
Feeding high dietary zinc to gestating sows and implications on sow and piglet performance, their biological responses, and the environment
(2023-10) Hammers, Kelsey
High rates of pre-weaning mortality continue to trouble the swine industry. Feeding high dietary concentrations of zinc (Zn) to sows during late gestation may have utility as a fetal imprinting strategy to positively influence their offspring and mitigate these piglet losses. Supplemental zinc fed in previous experiments were fed in a topdress form that required additional labor. With an aim to determine a practical zinc supplementation approach, a commercial sow study was conducted to investigate the effects of two Zn supplementation methods on sow and piglet performance and piglet mortality. Research in chapter 3 revealed that feeding elevated Zn to sows throughout gestation increased the proportion of pigs born alive, suggesting that elevated gestational Zn intake makes piglets more robust to endure the stresses of farrowing and decreases intrapartum mortality. While supplemental Zn may positively impact piglet performance, the mode through which high Zn acts is unknown. This dissertation aims to investigate three possible modes of action that may explain the influence of zinc on fetal imprinting and ultimately piglet survival. Research presented in chapter 4 indicates that high dietary Zn concentration elicited minimal changes on mineral concentrations of various tissues and serum from sows and piglets. Additionally, elevated Zn fed to sows minimally influenced gene expression of their low birth weight offspring. Research in chapter 5 characterized the effect of high dietary zinc on the microbiome of sows and piglets. Elevated dietary zinc fed to pregnant sows increased prevalence of intestinal bacteria that can be pathogenic in their offspring and favored microbes active in carbohydrate fermentation. Public and governmental concern regarding potential negative impacts of high dietary Zn has increased. Chapter 6 demonstrates that feeding high Zn to gestating sows will increase the amount of Zn excreted. However, the observed performance benefits of feeding high dietary Zn levels may partially offset its negative environmental footprint. This dissertation investigates possible biological mechanisms that high dietary Zn may work through to improve piglet survival and the possible environmental impact of feeding high Zn to gestating sows.
Gut microbial community structure in patients with chronic pancreatitis before and after total pancreatectomy with islet autotransplantation.
(2020-10) McEachron, Kendall
Chronic pancreatitis (CP) is characterized by abdominal pain, recurrent hospitalizations, frequent exposure to antibiotics, nutritional deficiencies, and chronic opioid use. Data describing the gut microbial community structure of patients with CP is limited. We aimed to compare gut microbial community structure of a group of patients with severe CP being considered for total pancreatectomy with islet autotransplantation (TPIAT) to that of healthy controls, and to associate these changes with the severity of clinical symptoms. We collected stool samples from healthy donors (n = 14) and patients with CP under consideration for TPIAT (n = 20), in addition to clinical metadata and a clinically validated abdominal symptoms severity survey. Patients with CP had, on average, significantly lower alpha diversity than healthy controls (P < 0.001). There was a significantly increased mean relative abundance of Faecalibacterium in healthy controls compared with CP (P = 0.02). Among participants with CP, those with a lower alpha diversity reported significantly worse functional abdominal symptoms (P = 0.006). These findings indicate that changes in gut microbial community structure may contribute to CP symptom severity, and provide a basis for future studies on whether enrichment of healthy commensal bacteria such as Faecalibacterium could provide clinically meaningful improvement in outcomes for patients with CP.
Gut microbiome westernization in Hmong and Karen refugees and immigrants in the United States
(2018-08) VANGAY, PAJAU
Many United States 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 U.S. immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the U.S., including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 U.S.-born Caucasian individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the U.S. is associated with immediate loss of gut microbiome diversity and function, with U.S.-associated strains and functions displacing native strains and functions. These effects increase with duration of U.S. residence, and are compounded by obesity and across generations.
Human Immunodeficiency Virus and Soil Transmitted Helminths: Measuring the Systemic Effects of Co-Infection in a Low-Resource Context
(2017-04) Morawski, Bozena
The impacts of helminth infection and anthelmintic therapy among HIV-infected people in co-endemic areas remains unknown. Health effects are likely species-dependent, and each species may exert countervailing effects on its host. Furthermore, there is a dearth of high-quality research conducted in the era of widely available ART. Data from two studies conducted in Mbale, Uganda were used to: 1) estimate clinical correlates of helminth infection among HIV-infected Ugandans; 2) characterize fecal microbiome composition in these participants, and correlate clinical characteristics with microbiome composition; and 3) evaluate the impact of anthelmintic therapy on markers of systemic inflammation in HIV-infected Ugandans via a randomized control trial. Aim I uses molecular methods to describe the prevalence and burden of 5 soil-transmitted helminth species among patients in outpatient HIV care, and quantifies the relationship between baseline helminth infection and immune status. We observed a clinically significant inverse relationship between hookworm infection and CD4+ T cells/mcL. Aim II analyses the fecal microbiome of HIV-infected Ugandans to identify differences in community structure across clinical characteristics, and determine if gut community structure and/or taxa are associated with change in immune status over time. Our results indicate lower bacterial community richness among participants with <100 CD4+ T cells/mcL, and identify two taxa that may be linked to CD4+ T cell recovery. Aim III quantifies changes in soluble CD14, C-reactive protein, and 10 pro-inflammatory cytokines in ART-initiated Ugandans randomized to either immediate or delayed albendazole therapy. Our findings indicate low helminth infection prevalence (10%) and an increase in soluble CD14 after 1-month of follow-up among participants receiving immediate albendazole. These aims contribute to knowledge of clinical and sub-clinical correlates of helminth infection in the ART era. Results may support integration of anthelmintic therapy into adult HIV care, which is often overlooked when setting anthelmintic program priorities.
Investigation of the microbiomes in two full-scale drinking water distribution systems
(2018-08) Waak, Michael
The drinking water distribution system (DWDS) microbiome can impact public health as well as distribution infrastructure. Though the majority of bacterial biomass in the DWDS is associated with biofilms on the walls of water mains and other surfaces, there is a lack of understanding about the biofilms due to the challenges of accessing them. Using culture-independent methods targeting marker genes, including real-time quantitative polymerase chain reaction (qPCR) and high-throughput sequencing of PCR amplicons, the microbiomes of two full-scale systems were investigated—a DWDS in the United States that maintains a chloramine residual and another in Norway that intentionally has very low or no residual disinfectant in the distributed water. This work demonstrates that residual chloramine is a fundamental factor affecting the microbiome in a chloraminated DWDS. Not all changes to the microbiome due to chloramine, however, may be desirable. Namely, non-tuberculous mycobacteria (NTM) and ammonia-oxidizing bacteria (AOB) in water-main biofilms benefit from residual chloramine, and both of these taxa pose possible concerns to water utilities and their consumers: NTM include some opportunistic pathogens (especially Mycobacterium avium complex, or MAC), and AOB may contribute to biologically accelerated chloramine decay. Still, chloramine appeared to generally work as desired. Biofilm biomass was significantly lower in the chloraminated DWDS, despite ostensibly more favorable conditions for bacterial growth, and most taxa in the bulk drinking water were not observed in the biofilms. Legionellae, which may include some opportunistic pathogens, were significantly reduced from the biofilms of the chloraminated DWDS, and no MAC were detected in either system. Characterization of the NTM indicated nearly all in the chloraminated DWDS were Mycobacterium gordonae-like species, while various phylogenetically-different species of novel NTM were present in the no-residual DWDS. Chloramine-derived ammonia also appeared to support an AOB community in the chloraminated DWDS comprised primarily of Nitrosomonas oligotropha-like taxa. Abiotic reaction of nitrite with the chloramine likely hinders complete biotic nitrification; nitrite-oxidizing bacteria (NOB) are denied available nitrite. Conversely, AOB, NOB, and ammonia-oxidizing archaea were all present in the no-residual DWDS despite little or no ammonia in the drinking water. Finally, corrosion-associated bacteria like Desulfovibrio spp. were common underneath corrosion tubercles in both systems. Microbiological activity may therefore contribute to corrosion of cast-iron water mains, regardless of whether a disinfectant residual is maintained in the bulk drinking water. This work provides novel evidence that residual chloramine alters the DWDS microbiome by reducing total biomass and diversity of water-main —though the remaining taxa may still pose management challenges. Future work will need to expand this type of research to other systems before general applicability to other systems can be assumed.
Multi-omics of host-microbiome interactions in human diseases
(2021-10) Priya, Sambhawa
While host genetics and gut microbiome have separately been identified as contributing factors to human health and disease, it is unclear how interactions between the two might drive disease risk. The modulation of host gene expression by the gut microbiome has been demonstrated as a potential mechanism by which microbes can affect host physiology. Therefore, understanding the molecular interactions between the microbiome and host gene regulation is critical for unravelling their contribution to the etiology of human diseases. Here, we comprehensively characterize functional interactions between the gut microbiome and host gene regulation across diverse human diseases to understand how these complex interactions might contribute to host pathophysiology. First, we characterized interactions between the gut mucosal microbiome and host gene expression in the colon of patients with cystic fibrosis to elucidate the potential role of host-microbiome interactions in the etiology of colorectal cancer in cystic fibrosis. Next, we developed a machine learning-based framework to jointly analyze host transcriptomic and microbiome profiles from colonic mucosal samples of patients with colorectal cancer, inflammatory bowel disease, and irritable bowel syndrome. We identified potential interactions between gut microbes and host genes that are disease-specific, as well as interactions that are shared across the three diseases, involving host genes and gut microbes previously implicated in gastrointestinal inflammation, gut barrier protection, energy metabolism, and tumorigenesis. We further adapted this integration framework to characterize multi-omic interactions between host gene expression, gut microbiome, and gut metabolome in irritable bowel syndrome. We also developed and applied supervised learning models to characterize patterns of host-microbiota interactions in diverse contexts to reveal microbial mediators of ethnic health disparities in the United States, and bacterial modulators of susceptibility to konzo in the Democratic Republic of the Congo. By identifying the host-microbiome interactions associated with human health and disease, results from our work can facilitate new insights into the molecular mechanisms by which microbiota impacts host health, and potentially lead to biomarkers for diagnostic and therapeutic interventions.
Relationships between cecum, ileum and litter bacterial microbiomes in a commercial turkey flock, and the impact of penicillin treatment on early bacterial community establishment
(2015-10-19) Danzeisen, Jessica; Clayton, Jonathan; Huang, Hu; Knights, Dan; McComb, Brian; Hayer, Shivdeep; Johnson, Timothy; joh04207@umn.edu; Johnson, Timothy
Gut health is paramount for commercial poultry production, and methods to assess gut health are critically needed to better understand how the avian gastrointestinal tract matures over time. One important aspect of gut health is the totality of bacterial populations inhabiting different sites of the avian gastrointestinal tract, and associations of these populations with the poultry farm environment, since these bacteria are thought to drive metabolism and prime the host immune system. In this study, a single flock of commercial turkeys was followed over the course of twelve weeks to examine bacterial microbiome inhabiting the ceca, ileum, and corresponding poultry litter. Furthermore, the effects of low-dose, growth-promoting penicillin treatment (50 g/ton) in feed on the ileum bacterial microbiome were also examined during the early brood period. The cecum and ileum bacterial communities of birds shifted independently but in parallel to one another over time, with distinct bacterial populations harboring each site. Corresponding poultry litter more closely represented the ileal bacterial populations than cecal bacterial populations, and also changed parallel to ileum bacterial populations over time. Penicillin applied at low doses in feed significantly enhanced early weight gain in commercial poults, and this correlated with predictable shifts in the ileum bacterial populations in control versus treatment groups. Overall, this study demonstrates the dynamic shifts in the turkey gastrointestinal microbiome during development, the correlations between bacterial populations in the gastrointestinal tract and the litter environment, and the impact of low-dose penicillin on the modulation of bacterial communities in the ileum. Alternatives to low-dose antibiotics would benefit by mimicking these effects in the gut, among others.
Seasonal Variations In The Activated Sludge Microbiome With Respect To Seasonal Nitrification Failure
(2020-07) Johnston, Juliet
Activated sludge consists of a diverse microbial community that is used by wastewater engineers to metabolize excessive nutrients in domestic wastewater so that these excessive nutrients do not impact downstream waters. While most biological contaminant removal processes, such as carbon (measured as Biological Oxygen Demand) and phosphorous removal are performed consistently year-round, nitrification performance significantly declines in cold temperatures. The seasonal decline in nitrification performance is known as seasonal nitrification failure. To understand seasonal nitrification failure, this thesis analyzed triplicate, full-scale, sequencing batch reactors throughout several years to investigate seasonal variations in the activated sludge microbiome with respect to community composition (16S rRNA gene), the metabolically active composition (16S rRNA transcript), and expression of amoA (ammonia monooxygenase) which is a key-nitrification functional gene. There were 114 OTUs (operational taxonomic units), which were consistently present in all three reactors, every week, for an entire year and together comprise 74.3% - 84.0% of the entire community. The changes in abundances of these OTUs and other seasonally present OTUs make each season’s community significantly distinct from each other. The community composition was also significantly distinct from the protein-synthesis composition throughout the entire year. While the entire activated sludge community and protein-synthesis compositions fluctuated, the ammonia-oxidizing community was at a constant abundance throughout the year based on tracking known ammonia oxidizers and the amoA functional gene despite seasonal nitrification failure. While the amoA transcripts declined with the seasonally cold temperatures, which explain the seasonal nitrification failure’s decline in activity, the known-ammonia oxidizer protein-synthesis potential measured by Nitrosomonas sp. 16S rRNA transcripts did not significantly decline with temperature. This suggests there are other metabolic activities performed by the known ammonia oxidizing community to maintain stable community abundance and protein synthesis potential when ammonia oxidization is no longer the most thermodynamically favorable metabolism. This result changes the narrative that seasonal nitrification failure occurs due to declining abundances of ammonia oxidizing organisms in cold temperatures, and instead provides insight as to how amoA expression seasonally changes with the complex and seasonally dynamic microbial ecology of the activated sludge community. Additionally, this research provides the most comprehensive baseline of the activated sludge communities seasonal composition, protein-synthesis potential and amoA expression to date. Future researchers can use these results to investigate specific highlighted seasonally variant OTUs which may influent the activated sludge microbiome, as well as explore the additional roles known ammonia oxidizers play in this complex microbial system.
Sulfur bacteria promote dissolution of authigenic carbonates at marine methane seeps
(2021-01-27) Leprich, Dalton J.; Flood, Beverly E.; Schroedl, Peter R.; Ricci, Elizabeth; Marlow, Jeffery J.; Girguis, Peter R.; Bailey, Jake V.; beflood@umn.edu; Flood, Beverly E.; University of Minnesota Bailey Geobiology Lab
Carbonate rocks at marine methane seeps are commonly colonized by sulfur-oxidizing bacteria that co-occur with etch pits that suggest active dissolution. We show that sulfur-oxidizing bacteria are abundant on the surface of an exemplar seep carbonate collected from Del Mar East Methane Seep Field, USA. We then used bioreactors containing aragonite mineral coupons that simulate certain seep conditions to investigate plausible in situ rates of carbonate dissolution associated with sulfur-oxidizing bacteria. Bioreactors inoculated with a sulfur-oxidizing bacterial strain, Celeribacter baekdonensis LH4, growing on aragonite coupons induced dissolution rates in sulfidic, heterotrophic, and abiotic conditions of 1773.97 (±324.35), 152.81 (±123.27), and 272.99 (±249.96) Mol CaCO3  cm-2  yr-1, respectively. Steep gradients in pH were also measured within carbonate-attached biofilms using pH-sensitive fluorophores. Together, these results show that the production of acidic microenvironments in biofilms of sulfur-oxidizing bacteria are capable of dissolving carbonate rocks, even under well-buffered marine conditions. Our results support the hypothesis that authigenic carbonate rock dissolution driven by lithotrophic sulfur-oxidation constitutes a previously unknown carbon flux from the rock reservoir to the ocean and atmosphere.
Using public data to evaluate global dynamics in biology publishing and the human microbiome
(2022-02) Abdill, Richard
The last decade has seen a rapid growth of research interest in the human microbiome, the bacterial communities that live on and in human bodies. Complex dynamics in the world of academic publishing have changed over almost the same period, during which time it has become increasingly common for researchers in the life sciences to share their manuscripts online as “preprints,” making them freely available prior to conventional peer review. Both are analyzed here by using publicly available data to quantify trends, patterns, and risks developing in both systems. First, I evaluate the growth of preprints posted to bioRxiv.org in its first five years. I describe the process for compiling the first comprehensive characterization of biology preprints and evaluate patterns in readership and outcomes for more than 37,000 manuscripts. Secondly, I examine changing trends in country-level preprint authorship and find patterns of international collaboration that suggest the supposedly egalitarian practice of preprinting may be replicating some of the same entrenched power dynamics found in conventional publishing. Third, I apply a similar approach to metadata for publicly available human microbiome samples: I characterize the origins of more than 440,000 samples and use country-level research activity to determine which countries are overrepresented in the characterization of the human microbiome relative to their population. Finally, I describe how we used this metadata in the construction of the largest human gut microbiome dataset in the world, consisting of more than 170,000 samples in one unified dataset that can be used to characterize broad patterns in microbial ecological dynamics.

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