Publications -- Yan Zhang

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This collection is limited to articles published under the terms of a creative commons license or other open access publishing agreement since 2016. It is not intended as a complete list of the author's works.


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    Suppression of host humoral immunity by Borrelia burgdorferi varies over the course of infection
    (American Society for Microbiology, 2024-03-22) Williams, Megan T.; Zhang, Yan; Pulse, Mark E.; Berg, Rance E.; Allen, Michael S.
    Borrelia burgdorferi, the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enables it to chronically persist in the host. The resulting immune response is characterized by unusually strong IgM production and a lack of long-term protective immunity. Previous studies in mice have shown that infection with B. burgdorferi also broadly suppresses host antibody responses against unrelated antigens. Here, we show that mice infected with B. burgdorferi and concomitantly immunized with recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein had an abrogated antibody response to the immunization. To further define how long this humoral immune suppression lasts, mice were immunized at 2, 4, and 6 weeks post-infection. Suppression of host antibody production against the SARS-CoV-2 spike protein peaked at 2 weeks post-infection but continued for all timepoints measured. Antibody responses against the SARS-CoV-2 spike protein were also assessed following antibiotic treatment to determine whether this immune suppression persists or resolves following clearance of B. burgdorferi. Host antibody production against the SARS-CoV-2 spike protein returned to baseline following antibiotic treatment; however, anti-SARS-CoV-2 IgM remained high, comparable to levels found in B. burgdorferi-infected but untreated mice. Thus, our data demonstrate restored IgG responses following antibiotic treatment but persistently elevated IgM levels, indicating lingering effects of B. burgdorferi infection on the immune system following treatment.
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    A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice
    (MDPI, 2023-11-25) Mancilla, Viviana J.; Braden-Kuhle, Paige N.; Brice, Kelly N.; Mann, Allison E.; Williams, Megan T.; Zhang, Yan; Chumley, Michael J.; Barber, Robert C.; White, Sabrina N.; Boehm, Gary W.; Allen, Michael S.
    The effects of synthetic, free-amino acid diets, similar to those prescribed as supplements for (phenylketonuria) PKU patients, on gut microbiota and overall health are not well understood. In the current, multidisciplinary study, we examined the effects of a synthetically-derived, low-fiber, amino acid diet on behavior, cognition, gut microbiome composition, and inflammatory markers. A cohort of 20 male C57BL/6J mice were randomly assigned to either a standard or synthetic diet (n = 10) at post-natal day 21 and maintained for 13 weeks. Sequencing of the 16S rRNA gene from fecal samples revealed decreased bacterial diversity, increased abundance of bacteria associated with disease, such as Prevotella, and a downward shift in gut microbiota associated with fermentation pathways in the synthetic diet group. Furthermore, there were decreased levels of short chain fatty acids and shortening of the colon in mice consuming the synthetic diet. Finally, we measured TNF-alpha, IL-6, and IL-10 in serum, the hippocampus, and colon, and found that the synthetic diet significantly increased IL-6 production in the hippocampus. These results demonstrate the importance of a multidisciplinary approach to future diet and microbiome studies, as diet not only impacts the gut microbiome composition but potentially systemic health as well.
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    The devil is in the details: Variable impacts of season, BMI, sampling site temperature, and presence of insects on the post-mortem microbiome
    (Frontiers Media S.A., 2022-12-27) Tarone, Aaron M.; Mann, Allison E.; Zhang, Yan; Zascavage, Roxanne R.; Mitchell, Elizabeth A.; Morales, Edgar; Rusch, Travis W.; Allen, Michael S.
    BACKGROUND: Post-mortem microbial communities are increasingly investigated as proxy evidence for a variety of factors of interest in forensic science. The reported predictive power of the microbial community to determine aspects of the individual's post-mortem history (e.g., the post-mortem interval) varies substantially among published research. This observed variation is partially driven by the local environment or the individual themselves. In the current study, we investigated the impact of BMI, sex, insect activity, season, repeat sampling, decomposition time, and temperature on the microbial community sampled from donated human remains in San Marcos, TX using a high-throughput gene-fragment metabarcoding approach. MATERIALS AND METHODS: In the current study, we investigated the impact of BMI, sex, insect activity, season, repeat sampling, decomposition time, and temperature on the microbial community sampled from donated human remains in San Marcos, TX using a high-throughput gene-fragment metabarcoding approach. RESULTS: We found that season, temperature at the sampling site, BMI, and sex had a significant effect on the post-mortem microbiome, the presence of insects has a homogenizing influence on the total bacterial community, and that community consistency from repeat sampling decreases as the decomposition process progresses. Moreover, we demonstrate the importance of temperature at the site of sampling on the abundance of important diagnostic taxa. CONCLUSION: The results of this study suggest that while the bacterial community or specific bacterial species may prove to be useful for forensic applications, a clearer understanding of the mechanisms underpinning microbial decomposition will greatly increase the utility of microbial evidence in forensic casework.
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    Hurricane Harvey Impacts on Water Quality and Microbial Communities in Houston, TX Waterbodies
    (Frontiers Media S.A., 2022-06-14) LaMontagne, Michael G.; Zhang, Yan; Guillen, George J.; Gentry, Terry J.; Allen, Michael S.
    Extreme weather events can temporarily alter the structure of coastal systems and generate floodwaters that are contaminated with fecal indicator bacteria (FIB); however, every coastal system is unique, so identification of trends and commonalities in these episodic events is challenging. To improve our understanding of the resilience of coastal systems to the disturbance of extreme weather events, we monitored water quality, FIB at three stations within Clear Lake, an estuary between Houston and Galveston, and three stations in bayous that feed into the estuary. Water samples were collected immediately before and after Hurricane Harvey (HH) and then throughout the fall of 2017. FIB levels were monitored by culturing E. coli and Enterococci. Microbial community structure was profiled by high throughput sequencing of PCR-amplified 16S rRNA gene fragments. Water quality and FIB data were also compared to historical data for these water body segments. Before HH, salinity within Clear Lake ranged from 9 to 11 practical salinity units (PSU). Immediately after the storm, salinity dropped to < 1 PSU and then gradually increased to historical levels over 2 months. Dissolved inorganic nutrient levels were also relatively low immediately after HH and returned, within a couple of months, to historical levels. FIB levels were elevated immediately after the storm; however, after 1 week, E. coli levels had decreased to what would be acceptable levels for freshwater. Enterococci levels collected several weeks after the storm were within the range of historical levels. Microbial community structure shifted from a system dominated by Cyanobacteria sp. before HH to a system dominated by Proteobacteria and Bacteroidetes immediately after. Several sequences observed only in floodwater showed similarity to sequences previously reported for samples collected following Hurricane Irene. These changes in beta diversity corresponded to salinity and nitrate/nitrite concentrations. Differential abundance analysis of metabolic pathways, predicted from 16S sequences, suggested that pathways associated with virulence and antibiotic resistance were elevated in floodwater. Overall, these results suggest that floodwater generated from these extreme events may have high levels of fecal contamination, antibiotic resistant bacteria and bacteria rarely observed in other systems.
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    Effects of temperature on bacterial microbiome composition in Ixodes scapularis ticks
    (John Wiley & Sons, Inc., 2018-09-21) Thapa, Santosh; Zhang, Yan; Allen, Michael S.
    Ixodes scapularis, the blacklegged deer tick, is the principal vector of Lyme disease in North America. Environmental factors are known to influence regional and seasonal incidence of Lyme disease and possibly the endemicity of the disease to the northeastern and upper mid-western regions of the United States. With a goal to understand the impact of environmental temperature on microbial communities within the tick, we investigated the bacterial microbiome of colony-reared I. scapularis ticks statically incubated at different temperatures (4, 20, 30, and 37°C) at a constant humidity in a controlled laboratory setting by comparison of sequenced amplicons of the bacterial 16S V4 rRNA gene to that of the untreated baseline controls. The microbiomes of colony-reared I. scapularis males were distinct than that of females, which were entirely dominated by Rickettsia. In silico removal of Rickettsia sequences from female data revealed the underlying bacterial community, which is consistent in complexity with those seen among male ticks. The bacterial community composition of these ticks changes upon incubation at 30°C for a week and 37°C for more than 5 days. Moreover, the male ticks incubated at 30 and 37°C exhibited significantly different bacterial diversity compared to the initial baseline microbiome, and the change in bacterial diversity was dependent upon duration of exposure. Rickettsia-free data revealed a significantly different bacterial diversity in female ticks incubated at 37°C compared to that of 4 and 20°C treatments. These results provide experimental evidence that environmental temperature can impact the tick bacterial microbiome in a laboratory setting.
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    Comparison of the Bacterial Gut Microbiome of North American Triatoma spp. With and Without Trypanosoma cruzi
    (Frontiers Media S.A., 2020-03-13) Mann, Allison E.; Mitchell, Elizabeth A.; Zhang, Yan; Curtis-Robles, Rachel; Thapa, Santosh; Hamer, Sarah A.; Allen, Michael S.
    Chagas disease, caused by the hemoflagellate protist Trypanosoma cruzi, affects nearly 6 million people worldwide, mainly in Latin America. Hematophagous triatomine insects ("kissing bugs") are the primary vectors of T. cruzi throughout the Americas and feed on a variety of animals, including humans. Control of triatomines is central to the control of T. cruzi infection. Recent advances in mitigation of other insect-borne diseases via the manipulation of insect-associated bacteria as a way to halt or slow disease transmission has opened questions to the applicability of these methods to Chagas disease vectors. Few studies have examined the hindgut microbiome of triatomines found in North America. In the current study, two species of triatomines were collected across Texas, United States, screened for the presence of T. cruzi, and analyzed for the bacterial composition of their hindguts using a 16S rRNA gene-fragment metabarcoding approach. We compared diversity of microbial community profiles across 74 triatomine insects to address the hypothesis that the richness and abundance of bacterial groups differ by T. cruzi infection and strain type, blood meal engorgement status, insect species, sex, and collection location. The gut microbial community of individual triatomines was characterized by low intraindividual taxonomic diversity and high interindividual variation that was weakly predicted by triatomine species, and was not predicted by triatomine sex, collection location, T. cruzi infection status, or blood meal score. However, we did find bacterial groups enriched in T. cruzi-positive individuals, including Enterobacterales, and Petrimonas. Additionally, we detected Salmonella enterica subspecies diarizonae in three triatomine individuals; this species is commonly associated with reptiles and domesticated animals and is a pathogen of humans. These data suggest that Triatoma spp. in Texas have variable patterns of colonized and transient bacteria, and may aid in development of novel means to interfere with transmission of the Chagas disease parasite T. cruzi. Deeper understanding of the effects of parasite infection on diverse insect vector microbiomes may highlight disease transmission risk and facilitate discovery of possible intervention strategies for biological control of this emerging vector-borne disease of global health significance.
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    Common Lung Microbiome Identified among Mechanically Ventilated Surgical Patients
    (PLOS, 2016-11-29) Smith, Ashley D.; Zhang, Yan; Barber, Robert C.; Minshall, Christian T.; Huebinger, Ryan M.; Allen, Michael S.
    The examination of the pulmonary microbiome in patients with non-chronic disease states has not been extensively examined. Traditional culture based screening methods are often unable to identify bacteria from bronchoalveolar lavage samples. The advancement of next-generation sequencing technologies allows for a culture-independent molecular based analysis to determine the microbial composition in the lung of this patient population. For this study, the Ion Torrent PGM system was used to assess the microbial complexity of culture negative bronchoalveolar lavage samples. A group of samples were identified that all displayed high diversity and similar relative abundance of bacteria. This group consisted of Hydrogenophaga, unclassified Bacteroidetes, Pedobacter, Thauera, and Acinetobacter. These bacteria may be representative of a common non-pathogenic pulmonary microbiome associated within this population of patients.
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    Bacterial microbiomes of Ixodes scapularis ticks collected from Massachusetts and Texas, USA
    (BioMed Central Ltd., 2019-06-24) Thapa, Santosh; Zhang, Yan; Allen, Michael S.
    BACKGROUND: The blacklegged tick, Ixodes scapularis, is the primary vector of the Lyme disease spirochete Borrelia burgdorferi in North America. Though the tick is found across the eastern United States, Lyme disease is endemic to the northeast and upper midwest and rare or absent in the southern portion of the vector's range. In an effort to better understand the tick microbiome from diverse geographic and climatic regions, we analysed the bacterial community of 115 I. scapularis adults collected from vegetation in Texas and Massachusetts, representing extreme ends of the vector's range, by massively parallel sequencing of the 16S V4 rRNA gene. In addition, 7 female I. scapularis collected from dogs in Texas were included in the study. RESULTS: Male I. scapularis ticks had a more diverse bacterial microbiome in comparison to the female ticks. Rickettsia spp. dominated the microbiomes of field-collected female I. scapularis from both regions, as well as half of the males from Texas. In addition, the male and female ticks captured from Massachusetts contained high proportions of the pathogens Anaplasma and Borrelia, as well as the arthropod endosymbiont Wolbachia. None of these were found in libraries generated from ticks collected in Texas. Pseudomonas, Acinetobacter and Mycobacterium were significantly differently abundant (p < 0.05) between the male ticks from Massachusetts and Texas. Anaplasma and Borrelia were found in 15 and 63% of the 62 Massachusetts ticks, respectively, with a co-infection rate of 11%. Female ticks collected from Texas dogs were particularly diverse, and contained several genera including Rickettsia, Pseudomonas, Bradyrhizobium, Sediminibacterium, and Ralstonia. CONCLUSIONS: Our results indicate that the bacterial microbiomes of I. scapularis ticks vary by sex and geography, with significantly more diversity in male microbiomes compared to females. We found that sex plays a larger role than geography in shaping the composition/diversity of the I. scapularis microbiome, but that geography affects what additional taxa are represented (beyond Rickettsia) and whether pathogens are found. Furthermore, recent feeding may have a role in shaping the tick microbiome, as evident from a more complex bacterial community in female ticks from dogs compared to the wild-caught questing females. These findings may provide further insight into the differences in the ability of the ticks to acquire, maintain and transmit pathogens. Future studies on possible causes and consequences of these differences will shed additional light on tick microbiome biology and vector competence.
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    The Adult Phenylketonuria (PKU) Gut Microbiome
    (MDPI, 2021-03-04) Mancilla, Viviana J.; Mann, Allison E.; Zhang, Yan; Allen, Michael S.
    Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism primarily treated through a phenylalanine-restrictive diet that is frequently supplemented with an amino acid formula to maintain proper nutrition. Little is known of the effects of these dietary interventions on the gut microbiome of PKU patients, particularly in adults. In this study, we sequenced the V4 region of the 16S rRNA gene from stool samples collected from adults with PKU (n = 11) and non-PKU controls (n = 21). Gut bacterial communities were characterized through measurements of diversity and taxa abundance. Additionally, metabolic imputation was performed based on detected bacteria. Gut community diversity was lower in PKU individuals, though this effect was only statistically suggestive. A total of 65 genera across 5 phyla were statistically differentially abundant between PKU and control samples (p < 0.001). Additionally, we identified six metabolic pathways that differed between groups (p < 0.05), with four enriched in PKU samples and two in controls. While the child PKU gut microbiome has been previously investigated, this is the first study to explore the gut microbiome of adult PKU patients. We find that microbial diversity in PKU children differs from PKU adults and highlights the need for further studies to understand the effects of dietary restrictions.
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    Variations of the lung microbiome and immune response in mechanically ventilated surgical patients
    (PLOS, 2018-10-24) Huebinger, Ryan M.; Smith, Ashley D.; Zhang, Yan; Monson, Nancy L.; Ireland, Sara J.; Barber, Robert C.; Kubasiak, John C.; Minshall, Christian T.; Minei, Joseph P.; Wolf, Steven E.; Allen, Michael S.
    Mechanically ventilated surgical patients have a variety of bacterial flora that are often undetectable by traditional culture methods. The source of infection in many of these patients remains unclear. To address this clinical problem, the microbiome profile and host inflammatory response in bronchoalveolar lavage samples from the surgical intensive care unit were examined relative to clinical pathology diagnoses. The hypothesis was tested that clinical diagnosis of respiratory tract flora were similar to culture positive lavage samples in both microbiome and inflammatory profile. Bronchoalveolar lavage samples were collected in the surgical intensive care unit as standard of care for intubated individuals with a clinical pulmonary infection score of >6 or who were expected to be intubated for >48 hours. Cytokine analysis was conducted with the Bioplex Pro Human Th17 cytokine panel. The microbiome of the samples was sequenced for the 16S rRNA region using the Ion Torrent. Microbiome diversity analysis showed the culture-positive samples had the lowest levels of diversity and culture negative with the highest based upon the Shannon-Wiener index (culture positive: 0.77 ± 0.36, respiratory tract flora: 2.06 ± 0.73, culture negative: 3.97 ± 0.65). Culture-negative samples were not dominated by a single bacterial genera. Lavages classified as respiratory tract flora were more similar to the culture-positive in the microbiome profile. A comparison of cytokine expression between groups showed increased levels of cytokines (IFN-g, IL-17F, IL-1B, IL-31, TNF-a) in culture-positive and respiratory tract flora groups. Culture-positive samples exhibited a more robust immune response and reduced diversity of bacterial genera. Lower cytokine levels in culture-negative samples, despite a greater number of bacterial species, suggest a resident nonpathogenic bacterial community may be indicative of a normal pulmonary environment. Respiratory tract flora samples were most similar to the culture-positive samples and may warrant classification as culture-positive when considering clinical treatment.