Kevin R. Theis

• PhD
• Professor (Associate) at Wayne State University

This editorial piece co-authored by the Senior Editors at Microbiome aims to highlight current challenges in the field of environmental and host-associated microbiome research. We also take the opportunity to clarify our expectations for the articles submitted to the journal. At Microbiome, we are seeking studies that provide either new mechanistic...

Sneathia vaginalis, a fastidious pathogen of the female reproductive tract, is implicated in obstetric and gynecologic pathologies, including spontaneous preterm birth and bacterial vaginosis. Here, we report the successful cultivation and genomic sequencing of three Sneathia vaginalis isolates collected via a vaginal swab from a patient with bacte...

Background: Cholera is a diarrheal disease prevalent in populations without access to clean water. Cholera is caused by Vibrio cholerae, which colonizes the upper small intestine in humans once ingested. A growing number of studies suggest that the gut microbiome composition modulates animal behavior. Zebrafish are an established cholera model that...

The bladder and urine have historically been considered sterile, especially in the context of clinical assessment. Yet, enhanced culture techniques and advances in DNA sequencing surveys have revealed a low microbial biomass microbiota in the bladders of most healthy individuals. Yet very few studies have investigated the urinary microbiota of preg...

Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PT...

Objectives To enable interactive visualization of the vaginal microbiome across the pregnancy and facilitate discovery of novel insights and generation of new hypotheses. Material and Methods Vaginal Microbiome Atlas during Pregnancy (VMAP) was created with R shiny to generate visualizations of structured vaginal microbiome data from multiple stud...

We present the results of 16S rRNA gene amplicon sequencing of the microbiota from preen oil and the cloaca of chipping sparrows (Spizella passerina) collected near Mountain Lake Biological Station in Pembroke, VA.

Cholera is a diarrheal disease prevalent in populations without access to clean water. Cholera is caused by Vibrio cholerae, which colonizes the upper small intestine in humans once ingested. A growing number of studies suggests the gut microbiome composition modulates animal behavior. Zebrafish are an established cholera model that can maintain a...

Background Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains un...

The field of microbial pathogenesis seeks to identify the agents and mechanisms responsible for disease causation. Since Robert Koch introduced postulates that were used to guide the characterization of microbial pathogens, technological advances have substantially increased the capacity to rapidly identify a causative infectious agent. Research ef...

The field of microbial pathogenesis seeks to identify the agents and mechanisms responsible for disease causation. Since Robert Koch introduced postulates that were used to guide the characterization of microbial pathogens, technological advances have substantially increased the capacity to rapidly identify a causative infectious agent. Research ef...

Preterm birth (PTB), commonly preceded by preterm labor, is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm labor are associated with sterile intra-amniotic inflammation (SIAI), an inflammatory condition without detectable microorganisms. To date, no successful strategies to treat SIAI have been developed. Her...

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals,...

Background Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment. Methods Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth...

Preterm birth, the leading cause of perinatal morbidity, often follows premature labor, a syndrome whose prevention remains a challenge. To better understand the relationship between premature labor and host-microbiome interactions, we conducted a mechanistic investigation using three preterm birth models. We report that intra-amniotic delivery of...

Cocaine is a highly addictive psychostimulant drug of abuse that constitutes an ongoing public health threat. Emerging research is revealing that numerous peripheral effects of this drug may serve as conditioned stimuli for its central reinforcing properties. The gut microbiota is emerging as one of these peripheral sources of input to cocaine rewa...

The composition of the vaginal microbiota is heavily influenced by pregnancy and may factor into pregnancy complications, including spontaneous preterm birth. However, results among studies have been inconsistent due, in part, to variation in sample sizes and ethnicity. Thus, an association between the vaginal microbiota and preterm labor continues...

Preterm birth (PTB), commonly preceded by preterm labor, is the leading cause of neonatal morbidity and mortality worldwide. Recent advances in next-generation sequencing have revealed that most cases of preterm labor are associated with sterile intra-amniotic inflammation (SIAI), an inflammatory condition without detectable microorganisms. To date...

The aim of this study was to establish the role of thymic stromal lymphopoietin (TSLP) in the intra-amniotic host response of women with spontaneous preterm labor (sPTL) and birth. Amniotic fluid and chorioamniotic membranes (CAM) were collected from women with sPTL who delivered at term (n = 30) or preterm without intra-amniotic inflammation (n =...

Objectives: This study was conducted to determine whether bacteria, fungi, or archaea are detected in the amniotic fluid of patients who underwent midtrimester amniocentesis for clinical indications. Methods: Amniotic fluid samples from 692 pregnancies were tested by using a combination of culture and end-point polymerase chain reaction (PCR) te...

The vaginal microbiome has been shown to be associated with pregnancy outcomes including preterm birth (PTB) risk. Here we present VMAP: Vaginal Microbiome Atlas during Pregnancy (http://vmapapp.org), an application to visualize features of 3,909 vaginal microbiome samples of 1,416 pregnant individuals from 11 studies, aggregated from raw public an...

The existence of a placental microbiota is debated. The human placenta has historically been considered sterile and microbial colonization was associated with adverse pregnancy outcomes. Yet, recent DNA sequencing investigations reported a microbiota in typical human term placentas. However, this detected microbiota could represent background DNA o...

Globally, every year about 11% of infants are born preterm, defined as a birth prior to 37 weeks of gestation, with significant and lingering health consequences. Multiple studies have related the vaginal microbiome to preterm birth. We present a crowdsourcing approach to predict: (a) preterm or (b) early preterm birth from 9 publicly available vag...

The composition of the vaginal microbiota is heavily influenced by pregnancy and may factor into pregnancy complications, including spontaneous preterm birth. However, results among studies have been inconsistent, due in part to variation in sample sizes and ethnicity. Thus an association between the vaginal microbiota and preterm labor continues t...

The intra-uterine components of labor, namely, myometrial contractility, cervical ripening, and decidua/membrane activation, have been extensively characterized and involve a local pro-inflammatory milieu of cellular and soluble immune mediators. Targeted profiling has demonstrated that such processes extend to the intra-amniotic space, yet unbiase...

The hologenome concept considers the entity formed by a host and its microbiota, the holobiont, as new level of hierarchical organization subject to neutral and selective forces. We used grafted plants to formally evaluate the hologenome concept. We analyzed the root-endosphere microbiota of two independent watermelon and grapevine plant systems, i...

Introduction Avian preen oil, secreted by the uropygial gland, is an important source of volatile compounds that convey information about the sender’s identity and quality, making preen oil useful for the recognition and assessment of potential mates and rivals. Although intrinsic factors such as hormone levels, genetic background, and diet can aff...

There is a gap in knowledge regarding the genomic diversity and variation of the gut microbiome across a host’s life span and across multiple generations of hosts in wild mammals. Using two types of sequencing approaches, we found that although gut microbiomes were individualized and temporally variable among hyenas, they correlated similarly to la...

Spontaneous preterm birth (sPTB) can occur when vaginal bacteria gain access to the amniotic cavity. Thus, the predictive value of the vaginal microbiota for sPTB has been investigated, yet results have been inconclusive. Here, we report the largest study of the vaginal microbiota using longitudinal sampling of 257 cases and 514 controls (2,976 sam...

The gut microbiome provides vital functions for mammalian hosts, yet research on the variability and function of the microbiome across adult lifespans and multiple generations is limited in large mammalian carnivores. Here we use 16S rRNA gene and metagenomic sequencing to profile the taxonomic composition, genomic diversity, and metabolic function...

Mice are widely utilized as animal models of obstetrical complications; however, the characterization of the murine microbiota during pregnancy has been neglected. Microorganisms from the vagina, oral cavity, intestine, and lung have been found in the intra-amniotic space, where their presence threatens the progression of gestation.

The existence of a placental microbiota is under debate. The human placenta has historically been considered sterile and microbial colonization has been associated with adverse pregnancy outcomes. Yet, recent investigations using DNA sequencing reported a microbiota in human placentas from typical term pregnancies. However, this detected microbiota...

Interferon epsilon (IFNe) is a recently described cytokine that is constitutively expressed in the female reproductive tract. However, the role of this hormonally-regulated cytokine during human pregnancy is poorly understood. Moreover, whether IFNe participates in host immune response against bacteria-driven intra-amniotic infection or cervical hu...

Whether the human placenta is a sterile organ is under debate. Yet, infection of the amniotic cavity, including the placenta, is causally linked to preterm birth. This study compares the bacterial profiles of term and preterm placentas through culture and 16S rRNA gene sequencing of the amnion, amnion-chorion interface, subchorion, villous tree, an...

In brief: The syndrome of preterm labor comprises multiple established and novel etiologies. This review summarizes the distinct immune mechanisms implicated in preterm labor and birth and highlights potential strategies for its prevention. Abstract: Preterm birth, the leading cause of neonatal morbidity and mortality worldwide, results from pre...

Objective To comprehensively characterize monocyte and neutrophil responses to E. coli and its product [lipopolysaccharide (LPS) or endotoxin] in vitro during pregnancy. Material or subjects Peripheral blood was collected from pregnant women during the third trimester (n = 20) and from non-pregnant women (n = 20). Methods The number, phagocytic a...

Mice are frequently used as animal models for mechanistic studies of infection and obstetrical disease, yet characterization of the murine microbiota during pregnancy is lacking. The objective of this study was to therefore characterize the microbiotas of distinct body sites of the pregnant mouse that harbor microorganisms that could potentially in...

The existence of an amniotic fluid microbiota (i.e., a viable microbial community) in mammals is controversial. Its existence would require a fundamental reconsideration of fetal in utero exposure to and colonization by microorganisms and the role of intra-amniotic microorganisms in fetal immune development as well as in pregnancy outcomes. In this...

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory...

Microbial invasion of the amniotic cavity (MIAC) leading to infection is strongly associated with adverse pregnancy and neonatal outcomes. Limitations of current diagnostic assays to detect MIAC rapidly and accurately have hindered the ability of obstetricians to identify and treat intra-amniotic infections. We developed, optimized, and validated t...

Zebrafish (Danio rerio) are an attractive model organism for a variety of scientific studies, including host-microbe interactions. Zebrafish contain a core (i.e., consistently detected) intestinal microbiome consisting primarily of Proteobacteria. Furthermore, this core intestinal microbiome is plastic, and can be significantly altered to due exter...

Zebrafish (Danio rerio) are an attractive model organism for a variety of scientific studies, including host-microbe interactions. The organism is particularly useful for the study of aquatic microbes that can colonize vertebrate hosts, including Vibrio cholerae, an intestinal pathogen. V. cholerae must colonize the intestine of an exposed host for...

The existence of an amniotic fluid microbiota (i.e., a viable microbial community) in mammals is controversial. Its existence would require a fundamental reconsideration of the role of intra-amniotic microbes in fetal development and pregnancy outcomes. In this study, we determined whether the amniotic fluid of mice harbors a microbiota in late ges...

Objectives: Intra-amniotic infection, defined by the presence of microorganisms in the amniotic cavity, is often accompanied by intra-amniotic inflammation. Occasionally, laboratories report the growth of bacteria or the presence of microbial nucleic acids in amniotic fluid in the absence of intra-amniotic inflammation. This study was conducted to...

Gulf war illness (GWI) is a chronic disorder of unknown etiology characterized by multiple symptoms such as pain, fatigue, gastrointestinal disturbances and neurocognitive problems. Increasing evidence suggests that gut microbiome perturbations play a key role in the pathology of this disorder. GWI courses with gut microbiota alterations and their...

The gut microbiota is critical for host function. Among mammals, host phylogenetic relatedness and diet are strong drivers of gut microbiota structure, but one factor may be more influential than the other. Here, we used 16S rRNA gene sequencing to determine the relative contributions of host phylogeny and host diet in structuring the gut microbiot...

Preterm labor precedes premature birth, the leading cause of neonatal morbidity and mortality worldwide. Preterm labor can either occur in the context of microbe-associated intra-amniotic inflammation (i.e. intra-amniotic infection) or intra-amniotic inflammation in the absence of detectable microorganisms (i.e. sterile intra-amniotic inflammation)...

Sneathia is an emerging pathogen implicated in adverse reproductive and perinatal outcomes. Although scarce, recent data suggest that vaginally residing Sneathia becomes pathogenic following its ascension into the upper urogenital tract, amniotic fluid, placenta, and foetal membranes. The role of Sneathia in women’s health and disease is generally...

Pregnant women are a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Herein, we report that SARS-CoV-2 infection during pregnancy primarily induced specific maternal in...

Objectives: Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5-12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amn...

The nematode Trichuris muris has been shown to interact with specific enteric bacteria, but its effects on the composition of its host's microbial community are not fully understood. We hypothesized that Trichuris muris-infected mice would have altered colon microbiota as compared with uninfected mice. Colon histopathology and microbial community s...

Dysregulation of the stress-induced activation of the hypothalamic-pituitary-adrenocortical axis can result in disease. Bidirectional communication exists between the brain and the gut, and alterations in these interactions appear to be involved in stress regulation and in the pathogenesis of neuropsychiatric diseases, such as depression. Serotonin...

Background: Recent studies suggest that alterations in the vaginal microbiome allow for the assessment of the risk for spontaneous preterm birth (PTB), the leading cause of neonatal morbidity and mortality worldwide. However, the associations between the local immune response and the vaginal microbiome are still poorly understood. Herein, we charac...

The gut microbiota is critical for host function. Among mammals, host phylogenetic relatedness and diet are strong drivers of gut microbiota structure, but one factor may be more influential than the other. Here, we used 16S rRNA gene sequencing to determine the relative contributions of host phylogeny and host dietary guild in structuring the gut...

Zebrafish (Danio rerio) are an attractive model organism for a variety of scientific studies, including host-microbe interactions. Zebrafish contain a core (i.e., consistently detected) intestinal microbiome consisting primarily of Proteobacteria. Furthermore, this core intestinal microbiome is plastic, and can be significantly altered to due exter...

Intra-amniotic infection is strongly associated with adverse pregnancy and neonatal outcomes. Most intra-amniotic infections are due to Ureaplasma species ; however, the pathogenic potency of these genital mycoplasmas to induce pre-term birth is still controversial. Here, we first laid out a taxonomic characterization of Ureaplasma isolates from wo...

Gulf War Illness (GWI) is a chronic health condition that appeared in Veterans after returning home from the Gulf War. The primary symptoms linked to deployment are posttraumatic stress disorder, mood disorders, GI problems and chronic fatigue. At first glance, these symptoms are difficult to ascribe to a single pathological mechanism. However, it...

Traumatic brain injury (TBI) is often accompanied by gastrointestinal and metabolic disruptions. These systemic manifestations suggest possible involvement of the gut microbiota in head injury outcomes. Although gut dysbiosis after single, severe TBI has been documented, the majority of head injuries are mild, such as those that occur in athletes a...

The prevailing paradigm in obstetrics has been the sterile womb hypothesis. However, some are asserting that the placenta, intra-amniotic environment, and fetus harbor microbial communities. The objective of this study was to determine whether the fetal and placental tissues of rhesus macaques harbor bacterial communities. Fetal, placental, and ute...

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every four preterm births is due to intra-amniotic infection, most commonly associated with Ureaplasma species. However, a causal link between Ureaplasma species and adverse pregnancy outcomes, as well as the triggered host immune responses, has not been invest...

Introduction: The existence of a placental microbiome would require a non-antagonistic relationship between potentially colonizing bacteria and trophoblasts. Objective: The immunologic response of trophoblasts to specific potentially invading bacteria needs further analysis. Methodology: Immortalized first trimester human trophoblasts Swan 71...

Rough-skinned newts (Taricha granulosa) use tetrodotoxin (TTX) to block voltage-gated sodium (Nav) channels as a chemical defense against predation. Interestingly, newts exhibit extreme population-level variation in toxicity attributed to a coevolutionary arms race with TTX-resistant predatory snakes, but the source of TTX in newts is unknown. Here...

Rough-skinned newts (Taricha granulosa) use tetrodotoxin (TTX) to block voltage-gated sodium (Nav) channels as a chemical defense against predation. Interestingly, newts exhibit extreme population-level variation in toxicity attributed to a coevolutionary arms race with TTX-resistant predatory snakes, but the source of TTX in newts is unknown. Here...

Rough-skinned newts (Taricha granulosa) use tetrodotoxin (TTX) to block voltage-gated sodium (Nav) channels as a chemical defense against predation. Interestingly, newts exhibit extreme population-level variation in toxicity attributed to a coevolutionary arms race with TTX-resistant predatory snakes, but the source of TTX in newts is unknown. Here...

The prevailing paradigm in obstetrics has been the sterile womb hypothesis. However, some are asserting that the placenta, intra-amniotic environment, and fetus harbor microbial communities. The objective of this study was to determine if the fetal and placental tissues of rhesus macaques harbor viable bacterial communities. Fetal, placental, and u...

The prevailing paradigm in obstetrics has been the sterile womb hypothesis, which posits that fetuses are first colonized by microorganisms during the delivery process. However, some are now suggesting that fetuses are consistently colonized in utero by microorganisms from microbial communities that inhabit the placenta and intra-amniotic environme...

The list of pharmacological agents that can modify the gut microbiome or be modified by it continues to grow at a high rate. The greatest amount of attention on drug-gut microbiome interactions has been directed primarily at pharmaceuticals used to treat infection, diabetes, cardiovascular conditions and cancer. By comparison, drugs of abuse and ad...

Background Intra-amniotic inflammation, which is associated with adverse pregnancy outcomes, can occur in the presence or absence of detectable microorganisms, and involves activation of the inflammasome. Intra-amniotic inflammasome activation has been reported in clinical chorioamnionitis at term and preterm labor with intact membranes, but it has...

The hologenome concept of evolution posits that animals and their symbiotic microbes are emergent individuals, or holobionts, exhibiting synergistic phenotypes that are subject to evolutionary forces. Its premises are that interactions between animals and their microbes affect the fitness of holobionts, in both beneficial and deleterious ways, and...

Host-associated microbial communities, henceforth 'microbiota', can affect the physiology and behavior of their hosts. In mammals, host ecological, social, and environmental variables are associated with variation in microbial communities. Within individuals in a given mammalian species, the microbiota also partitions by body-site. Here, we build o...

The existence of a placental microbiota and in utero colonization of the fetus has been the subject of recent debate. The objective of this study was to determine whether the placental and fetal tissues of mice harbor bacterial communities. Bacterial profiles of the placenta and fetal brain, lung, liver, and intestine were characterized through cul...

Background Microbial invasion of the amniotic cavity resulting in intra-amniotic infection is associated with obstetrical complications such as preterm labor with intact or ruptured membranes, cervical insufficiency, as well as clinical and histological chorioamnionitis. The most widely accepted pathway for intra-amniotic infection is the ascension...

Background Intestinal bacterial communities are not homogenous throughout the gastrointestinal tract. Human research on the gut microbiome often neglects intra-intestinal variability by relying on a single measurement from stool samples. One source of complexity is the adherence to undigested, residual fiber. Currently, no procedure exists to extra...

Symbiotic microbes that inhabit animal scent glands can produce volatile compounds used as chemical signals by the host animal. Though several studies have demonstrated correlations between scent gland bacterial community structure and host animal odour profiles, none have systematically demonstrated a causal relationship. In birds, volatile compou...

Recent molecular studies concluded that the endometrium has a resident microbiota dominated by Lactobacillus spp. and is therefore similar to that of the vagina. These findings were largely derived from endometrial samples obtained through a transcervical catheter and thus prone to contamination. Herein, we investigated the molecular microbial prof...

Zebrafish (Danio rerio) are an attractive model organism for scientific studies, including host-microbe interactions. The organism is particularly useful for studying aquatic microbes that can colonize vertebrate hosts, including Vibrio cholerae. Previous studies have established the presence of a core zebrafish intestinal microbiome, and tracked t...

The holobiont concept defines a given organism and its associated symbionts as a potential level of selection over evolutionary time. In clonal plants, recent experiments demonstrated vertical transmission of part of the microbiota from one ramet (i.e., potentially autonomous individual) to another within the clonal network (i.e., connections by mo...

Microbial communities within the soil of Laurentian Great Lakes coastal wetlands drive biogeochemical cycles and provide several other ecosystem services. However, there exists a lack of understanding of how microbial communities respond to nutrient gradients and human activity in these systems. This research sought to address the lack of understan...

BACKGROUND: The human placenta has been traditionally viewed as sterile, and microbial invasion of this organ has been associated with adverse pregnancy outcomes. Yet, recent studies that utilized sequencing techniques reported that the human placenta at term contains a unique microbiota. These conclusions are largely based on the results derived f...

Raw count data for operational taxonomic units, with the use of both 97% and 99% nucleotide similarity cutoffs, detected in placental tissues and background technical controls in the primary 16S rRNA gene analyses for this study.

Raw count data for placental tissue and background technical control metagenomic sequences at the genus level.