The zebrafish gut microbiome influences benzo[a]pyrene developmental neurobehavioral toxicity.

Early-life exposure to environmental toxicants like Benzo[a]pyrene (BaP) is associated with several health consequences in vertebrates (i.e., impaired or altered neurophysiological and behavioral development). Although toxicant impacts were initially studied relative to host physiology, recent studies suggest that the gut microbiome is a possible target and/or mediator of behavioral responses to chemical exposure in organisms, via the gut-brain axis. However, the connection between BaP exposure, gut microbiota, and developmental neurotoxicity remains understudied. Using a zebrafish model, we determined whether the gut microbiome influences BaP impacts on behavior development. Embryonic zebrafish were treated with increasing concentrations of BaP and allowed to grow to the larval life stage, during which they underwent behavioral testing and intestinal dissection for gut microbiome profiling via high-throughput sequencing. We found that exposure affected larval zebrafish microbiome diversity and composition in a manner tied to behavioral development: increasing concentrations of BaP were associated with increased taxonomic diversity, exposure was associated with unweighted UniFrac distance, and microbiome diversity and exposure predicted larval behavior. Further, a gnotobiotic zebrafish experiment clarified whether microbiome presence was associated with BaP exposure response and behavioral changes. We found that gut microbiome state altered the relationship between BaP exposure concentration and behavioral response. These results support the idea that the zebrafish gut microbiome is a determinant of the developmental neurotoxicity that results from chemical exposure.

Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults.

Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo. We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.

Microbiome ecological memory and responses to repeated marine heatwaves clarify variation in coral bleaching and mortality.

Microbiomes are essential features of holobionts, providing their hosts with key metabolic and functional traits like resistance to environmental disturbances and diseases. In scleractinian corals, questions remain about the microbiome's role in resistance and resilience to factors contributing to the ongoing global coral decline and whether microbes serve as a form of holobiont ecological memory. To test if and how coral microbiomes affect host health outcomes during repeated disturbances, we conducted a large-scale (32 exclosures, 200 colonies, and 3 coral species sampled) and long-term (28 months, 2018-2020) manipulative experiment on the forereef of Mo'orea, French Polynesia. In 2019 and 2020, this reef experienced the two most severe marine heatwaves on record for the site. Our experiment and these events afforded us the opportunity to test microbiome dynamics and roles in the context of coral bleaching and mortality resulting from these successive and severe heatwaves. We report unique microbiome responses to repeated heatwaves in Acropora retusa, Porites lobata, and Pocillopora spp., which included: microbiome acclimatization in A. retusa, and both microbiome resilience to the first marine heatwave and microbiome resistance to the second marine heatwave in Pocillopora spp. Moreover, observed microbiome dynamics significantly correlated with coral species-specific phenotypes. For example, bleaching and mortality in A. retusa both significantly increased with greater microbiome beta dispersion and greater Shannon Diversity, while P. lobata colonies had different microbiomes across mortality prevalence. Compositional microbiome changes, such as changes to proportions of differentially abundant putatively beneficial to putatively detrimental taxa to coral health outcomes during repeated heat stress, also correlated with host mortality, with higher proportions of detrimental taxa yielding higher mortality in A. retusa. This study reveals evidence for coral species-specific microbial responses to repeated heatwaves and, importantly, suggests that host-dependent microbiome dynamics may provide a form of holobiont ecological memory to repeated heat stress.

Sulforaphane and Sulforaphane-Nitrile Metabolism in Humans Following Broccoli Sprout Consumption: Inter-individual Variation, Association with Gut Microbiome Composition, and Differential Bioactivity.

SCOPE: The glucosinolate glucoraphanin from broccoli is converted to sulforaphane (SFN) or sulforaphane-nitrile (SFN-NIT) by plant enzymes or the gut microbiome. Human feeding studies typically observe high inter-individual variation in absorption and excretion of SFN, however, the source of this variation is not fully known. To address this, a human feeding trial to comprehensively evaluate inter-individual variation in the absorption and excretion of all known SFN metabolites in urine, plasma, and stool, and tested the hypothesis that gut microbiome composition influences inter-individual variation in total SFN excretion has been conducted. METHODS AND RESULTS: Participants (n = 55) consumed a single serving of broccoli or alfalfa sprouts and plasma, stool, and total urine are collected over 72 h for quantification of SFN metabolites and gut microbiome profiling using 16S gene sequencing. SFN-NIT excretion is markedly slower than SFN excretion (72 h vs 24 h). Members of genus Bifidobacterium, Dorea, and Ruminococcus torques are positively associated with SFN metabolite excretion while members of genus Alistipes and Blautia has a negative association. CONCLUSION: This is the first report of SFN-NIT metabolite levels in human plasma, urine, and stool following consumption of broccoli sprouts. The results help explain factors driving inter-individual variation in SFN metabolism and are relevant for precision nutrition.

Tenth Aquatic Models of Human Disease Conference 2022 Workshop Report: Aquatics Nutrition and Reference Diet Development.

Progress in biomedical research requires rigorous studies and reproducible outcomes. However, despite recent achievements, standard reference diets (SRDs) for aquatic model organisms, vital for supporting scientific rigor and reproducibility, are yet to be adopted. At this workshop, we presented findings from a 7-month diet test study, tightly coordinated and conducted across three aquatic research facilities: Zebrafish International Resource Center (ZIRC), Kent and Sharpton laboratories (Oregon State University), and Xiphophorus Genetic Stock Center (XGSC, Texas State University). We compared the impact of two commercial diets and a suggested zebrafish SRD on general fish husbandry, microbiome composition, and health in three fish species (zebrafish, Xiphophorus, and Medaka), and three zebrafish wild-type strains. We reported outcomes, gathered community feedback, and addressed the aquatic research community's need for SRD development. Discussions underscored the influence of diet on aquatic research variability, emphasizing the need for SRDs to control cross-experiment and cross-laboratory reproducibility. Species-specific reference diets are essential for model organism health and consistent research outcomes.

Identification of rare microbial colonizers of plastic materials incubated in a coral reef environment.

Plastic waste accumulation in marine environments has complex, unintended impacts on ecology that cross levels of community organization. To measure succession in polyolefin-colonizing marine bacterial communities, an in situ time-series experiment was conducted in the oligotrophic coastal waters of the Bermuda Platform. Our goals were to identify polyolefin colonizing taxa and isolate bacterial cultures for future studies of the biochemistry of microbe-plastic interactions. HDPE, LDPE, PP, and glass coupons were incubated in surface seawater for 11 weeks and sampled at two-week intervals. 16S rDNA sequencing and ATR-FTIR/HIM were used to assess biofilm community structure and chemical changes in polymer surfaces. The dominant colonizing taxa were previously reported cosmopolitan colonizers of surfaces in marine environments, which were highly similar among the different plastic types. However, significant differences in rare community composition were observed between plastic types, potentially indicating specific interactions based on surface chemistry. Unexpectedly, a major transition in community composition occurred in all material treatments between days 42 and 56 (p < 0.01). Before the transition, Alteromonadaceae, Marinomonadaceae, Saccharospirillaceae, Vibrionaceae, Thalassospiraceae, and Flavobacteriaceae were the dominant colonizers. Following the transition, the relative abundance of these taxa declined, while Hyphomonadaceae, Rhodobacteraceae and Saprospiraceae increased. Over the course of the incubation, 8,641 colonizing taxa were observed, of which 25 were significantly enriched on specific polyolefins. Seven enriched taxa from families known to include hydrocarbon degraders (Hyphomonadaceae, Parvularculaceae and Rhodobacteraceae) and one n-alkane degrader (Ketobacter sp.). The ASVs that exhibited associations with specific polyolefins are targets of ongoing investigations aimed at retrieving plastic-degrading microbes in culture.

Behavioral and Cognitive Performance Following Exposure to Second-Hand Smoke (SHS) from Tobacco Products Associated with Oxidative-Stress-Induced DNA Damage and Repair and Disruption of the Gut Microbiome.

Exposure to second-hand Smoke (SHS) remains prevalent. The underlying mechanisms of how SHS affects the brain require elucidation. We tested the hypothesis that SHS inhalation drives changes in the gut microbiome, impacting behavioral and cognitive performance as well as neuropathology in two-month-old wild-type (WT) mice and mice expressing wild-type human tau, a genetic model pertinent to Alzheimer's disease mice, following chronic SHS exposure (10 months to ~30 mg/m3). SHS exposure impacted the composition of the gut microbiome as well as the biodiversity and evenness of the gut microbiome in a sex-dependent fashion. This variation in the composition and biodiversity of the gut microbiome is also associated with several measures of cognitive performance. These results support the hypothesis that the gut microbiome contributes to the effect of SHS exposure on cognition. The percentage of 8-OHdG-labeled cells in the CA1 region of the hippocampus was also associated with performance in the novel object recognition test, consistent with urine and serum levels of 8-OHdG serving as a biomarker of cognitive performance in humans. We also assessed the effects of SHS on the percentage of p21-labeled cells, an early cellular marker of senescence that is upregulated in bronchial cells after exposure to cigarette smoke. Nuclear staining of p21-labeled cells was more prominent in larger cells of the prefrontal cortex and CA1 hippocampal neurons of SHS-exposed mice than in sham-exposed mice, and there was a significantly greater percentage of labelled cells in the prefrontal cortex and CA1 region of the hippocampus of SHS than air-exposed mice, suggesting that exposure to SHS may result in accelerated brain aging through oxidative-stress-induced injury.

Assessment of various standard fish diets on gut microbiome of platyfish Xiphophorus maculatus.

Diet is an external factor that affects the physiological baseline of research animals. It can shape gut microbiome, which can impact the host. As a result, dietary variation can challenge experimental reproducibility and data integration across studies when not appropriately considered. To control for diet-induced variation, reference diets have been developed for common biomedical models. However, such reference diets have not yet been developed for nontraditional model organisms, such as Xiphophorus species. In this study, we compared two diets designed for zebrafish, a commercial zebrafish diet (Gemma and GEM), and a proposed zebrafish reference diet developed by the Watts laboratory at the University of Alabama at Birmingham (WAT) to the Xiphophorus Genetic Stock Center custom diet (CON) to evaluate the influence of diet on the Xiphophorus gut microbiome. Xiphophorus maculatus were fed the three diets from 2 to 6 months of age. Feces were collected and the gut microbiome was assessed using 16S rRNA sequencing every month. We observed substantial diet-driven variation in the gut microbiome. Our results indicate that diets developed specifically for zebrafish can affect the gut microbiome composition and may not be optimal for Xiphophorus.

Gastrointestinal Dysfunction in Neurological and Neurodegenerative Disorders.

Increasing research links the gut microbiome to neurodegenerative disorders. The gut microbiome communicates with the central nervous system via the gut-brain axis and affects behavioral and cognitive phenotypes. Dysbiosis (a dysfunctional microbiome) drives increased intestinal permeability and inflammation that can negatively affect the brain via the gut-brain axis. Healthier metabolic and lipid profiles and cognitive phenotypes are observed in individuals with more distinct microbiomes. In this review, we discuss the role of the gut microbiome and gut-brain axis in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease and related animal models, in cancer and cancer treatments, and in metabolic syndrome. We also discuss strategies to improve the gut microbiome and ultimately brain function. Because healthier cognitive phenotypes are observed in individuals with more distinct microbiomes, increased efforts are warranted to develop therapeutic strategies for those at increased risk of developing neurological disorders and patients diagnosed with those disorders.

Disentangling the link between zebrafish diet, gut microbiome succession, and Mycobacterium chelonae infection.

BACKGROUND: Despite the long-established importance of zebrafish (Danio rerio) as a model organism and their increasing use in microbiome-targeted studies, relatively little is known about how husbandry practices involving diet impact the zebrafish gut microbiome. Given the microbiome's important role in mediating host physiology and the potential for diet to drive variation in microbiome composition, we sought to clarify how three different dietary formulations that are commonly used in zebrafish facilities impact the gut microbiome. We compared the composition of gut microbiomes in approximately 60 AB line adult (129- and 214-day-old) zebrafish fed each diet throughout their lifespan. RESULTS: Our analysis finds that diet has a substantial impact on the composition of the gut microbiome in adult fish, and that diet also impacts the developmental variation in the gut microbiome. We further evaluated how 214-day-old fish microbiome compositions respond to exposure of a common laboratory pathogen, Mycobacterium chelonae, and whether these responses differ as a function of diet. Our analysis finds that diet determines the manner in which the zebrafish gut microbiome responds to M. chelonae exposure, especially for moderate and low abundance taxa. Moreover, histopathological analysis finds that male fish fed different diets are differentially infected by M. chelonae. CONCLUSIONS: Overall, our results indicate that diet drives the successional development of the gut microbiome as well as its sensitivity to exogenous exposure. Consequently, investigators should carefully consider the role of diet in their microbiome zebrafish investigations, especially when integrating results across studies that vary by diet.

Dark-purple rice extract modulates gut microbiota composition in acetic acid– and indomethacin-induced inflammatory bowel disease in rats / El extracto de arroz púrpura oscuro modula la composición de la microbiota intestinal en la enfermedad inflamatoria intestinal inducida por ácido acético e indometacina en ratas

Ulcerative colitis (UC) and Crohn’s disease (CD) are two major forms of inflammatory bowel disease (IBD). The disease has been linked with gut microbiota dysbiosis in which the balance of commensal communities is disrupted. Accumulating evidence demonstrates that treatment with biologically active compounds can modulate gut microbiota composition in animal models. Our previous work has also shown the beneficial effect of Luem Pua (LP) rice extract, which is rich in anthocyanins, on inflammation. However, its effect on gut microbiota is yet to be explored. In this study, we profiled fecal microbiota of acetic acid (AA)–induced UC and indomethacin (ID)–induced CD rat models with and without pretreatment with LP rice extract by 16S rRNA gene sequencing. The results showed that gut microbiota communities of rats were altered by both AA-induced UC and ID-induced CD. The relative abundances of beneficial bacteria, especially the Lachnospiraceae NK4A136 group and Lactobacillus, were decreased in the AA-induced UC model, while some opportunistic pathogens (Bacteroides, Escherichia/Shigella, Fusobacterium, and Veillonella) were raised by ID-induced CD. Interestingly, pretreatment with LP rice extract before AA-inducing UC in rats increased the proportion of the butyrate-producing bacteria (Lachnospiraceae NK4A136 group). The abundances of these beneficial bacteria and other SCFA-producing bacteria were unaffected by the indomethacin treatment with LP. Overall, our study revealed different impacts of AA-induced UC and ID-induced CD on changes in community composition and hinted at how LP may protect against UC by modifying the gut microbiota.(AU)

Best practice for wildlife gut microbiome research: A comprehensive review of methodology for 16S rRNA gene investigations.

Extensive research in well-studied animal models underscores the importance of commensal gastrointestinal (gut) microbes to animal physiology. Gut microbes have been shown to impact dietary digestion, mediate infection, and even modify behavior and cognition. Given the large physiological and pathophysiological contribution microbes provide their host, it is reasonable to assume that the vertebrate gut microbiome may also impact the fitness, health and ecology of wildlife. In accordance with this expectation, an increasing number of investigations have considered the role of the gut microbiome in wildlife ecology, health, and conservation. To help promote the development of this nascent field, we need to dissolve the technical barriers prohibitive to performing wildlife microbiome research. The present review discusses the 16S rRNA gene microbiome research landscape, clarifying best practices in microbiome data generation and analysis, with particular emphasis on unique situations that arise during wildlife investigations. Special consideration is given to topics relevant for microbiome wildlife research from sample collection to molecular techniques for data generation, to data analysis strategies. Our hope is that this article not only calls for greater integration of microbiome analyses into wildlife ecology and health studies but provides researchers with the technical framework needed to successfully conduct such investigations.

Early detection of Pseudocapillaria tomentosa by qPCR in four lines of zebrafish, Danio rerio (Hamilton 1882).

The intestinal nematode Pseudocapillaria tomentosa in zebrafish (Danio rerio) causes profound intestinal lesions, emaciation and death and is a promoter of a common intestinal cancer in zebrafish. This nematode has been detected in zebrafish from about 15% of the laboratories. Adult worms are readily detected about 3 weeks after exposure by either histology or wet mount preparations of the intestine, and larval worms are inconsistently observed in fish before this time. A quantitative PCR (qPCR) test was recently developed to detect the worm in fish and water, and here we determined that the test on zebrafish intestines was effective for earlier detection. Four lines of zebrafish (AB, TU, 5D and Casper) were experimentally infected and evaluated by wet mounts and qPCR at 8, 15-, 22-, 31- and 44-day post-exposure (dpe). At the first two time points, only 8% of the wet mounts from exposed fish were identified as infected, while the same intestines screened by qPCR showed 78% positivity, with low and consistent cycle threshold (Ct) values at these times. Wet mounts at later time points showed a high prevalence of infection, but this was still surpassed by qPCR.

Colonic Microbial Abundances Predict Adenoma Formers.

OBJECTIVE: We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation. SUMMARY BACKGROUND DATA: Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions. METHODS: Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, nonadenoma and adenoma-adjacent mucosa were collected along with clinical and dietary information. 16S rRNA gene libraries were generated using V4 primers. DADA2 processed sequence reads and custom R-scripts quantified microbial diversity. Linear regression identified differential taxonomy and diversity in microbial communities and machine learning identified adenoma former microbial signatures. RESULTS: One hundred four subjects were included, 46% with adenomas. Mucosal and fecal samples were dominated by Firmicutes and Bacteroidetes whereas Firmicutes and Proteobacteria were most abundant in oral communities. Mucosal communities harbored significant microbial diversity that was not observed in fecal or oral communities. Random forest classifiers predicted adenoma formation using fecal, oral, and mucosal amplicon sequence variant (ASV) abundances. The mucosal classifier reliably diagnosed adenoma formation with an area under the curve (AUC) = 0.993 and an out-of-bag (OOB) error of 3.2%. Mucosal classifier accuracy was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. In contrast, classifiers built using fecal and oral samples manifested high OOB error rates (47.3% and 51.1%, respectively) and poor diagnostic abilities (fecal and oral AUC = 0.53). CONCLUSION: Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation.

Dark-purple rice extract modulates gut microbiota composition in acetic acid- and indomethacin-induced inflammatory bowel disease in rats.

Ulcerative colitis (UC) and Crohn's disease (CD) are two major forms of inflammatory bowel disease (IBD). The disease has been linked with gut microbiota dysbiosis in which the balance of commensal communities is disrupted. Accumulating evidence demonstrates that treatment with biologically active compounds can modulate gut microbiota composition in animal models. Our previous work has also shown the beneficial effect of Luem Pua (LP) rice extract, which is rich in anthocyanins, on inflammation. However, its effect on gut microbiota is yet to be explored. In this study, we profiled fecal microbiota of acetic acid (AA)-induced UC and indomethacin (ID)-induced CD rat models with and without pretreatment with LP rice extract by 16S rRNA gene sequencing. The results showed that gut microbiota communities of rats were altered by both AA-induced UC and ID-induced CD. The relative abundances of beneficial bacteria, especially the Lachnospiraceae NK4A136 group and Lactobacillus, were decreased in the AA-induced UC model, while some opportunistic pathogens (Bacteroides, Escherichia/Shigella, Fusobacterium, and Veillonella) were raised by ID-induced CD. Interestingly, pretreatment with LP rice extract before AA-inducing UC in rats increased the proportion of the butyrate-producing bacteria (Lachnospiraceae NK4A136 group). The abundances of these beneficial bacteria and other SCFA-producing bacteria were unaffected by the indomethacin treatment with LP. Overall, our study revealed different impacts of AA-induced UC and ID-induced CD on changes in community composition and hinted at how LP may protect against UC by modifying the gut microbiota.

Defining the environmental determinants of dysbiosis at scale with zebrafish.

The gut microbiome, critical to maintaining vertebrate homeostasis, is susceptible to a various exposures. In some cases, these exposures induce dysbiosis, wherein the microbiome changes into a state conducive to disease progression. To better prevent, manage, and treat health disorders, we need to define which exposures induce dysbiosis. Contemporary methods face challenges due to the immense diversity of the exposome and the restricted throughput of conventional experimental tools used for dysbiosis evaluation. We propose integrating high-throughput model systems as an augment to traditional techniques for rapid identification of dysbiosis-inducing agents. Although high-throughput screening tools revolutionized areas such as pharmacology and toxicology, their incorporation in gut microbiome research remains limited. One particularly powerful high-throughput model system is the zebrafish, which affords access to scalable in vivo experimentation involving a complex gut microbiome. Numerous studies have employed this model to identify potential dysbiosis triggers. However, its potential could be further harnessed via innovative study designs, such as evaluation of synergistic effects from combined exposures, expansions to the methodological toolkit to discern causal effects of microbiota, and efforts to assess and improve the translational relevance of the model. Ultimately, this burgeoning experimental resource can accelerate the discovery of agents that underlie dysbiotic disorders.

Chronic clinical signs of upper respiratory tract disease associate with gut and respiratory microbiomes in a cohort of domestic felines.

Feline upper respiratory tract disease (FURTD), often caused by infections etiologies, is a multifactorial syndrome affecting feline populations worldwide. Because of its highly transmissible nature, infectious FURTD is most prevalent anywhere cats are housed in groups such as animal shelters, and is associated with negative consequences such as decreasing adoption rates, intensifying care costs, and increasing euthanasia rates. Understanding the etiology and pathophysiology of FURTD is thus essential to best mitigate the negative consequences of this disease. Clinical signs of FURTD include acute respiratory disease, with a small fraction of cats developing chronic sequelae. It is thought that nasal mucosal microbiome changes play an active role in the development of acute clinical signs, but it remains unknown if the microbiome may play a role in the development and progression of chronic clinical disease. To address the knowledge gap surrounding how microbiomes link to chronic FURTD, we asked if microbial community structure of upper respiratory and gut microbiomes differed between cats with chronic FURTD signs and clinically normal cats. We selected 8 households with at least one cat exhibiting chronic clinical FURTD, and simultaneously collected samples from cohabitating clinically normal cats. Microbial community structure was assessed via 16S rDNA sequencing of both gut and nasal microbiome communities. Using a previously described ecophylogenetic method, we identified 136 and 89 microbial features within gut and nasal microbiomes respectively that significantly associated with presence of active FURTD clinical signs in cats with a history of chronic signs. Overall, we find that nasal and gut microbial community members associate with the presence of chronic clinical course, but more research is needed to confirm our observations.

A Non-Randomized Trial Investigating the Impact of Brown Rice Consumption on Gut Microbiota, Attention, and Short-Term Working Memory in Thai School-Aged Children.

While dietary fiber has been shown to influence the composition of gut microbiota and cognitive function in adults, much less is known about the fiber-microbiome-cognition association in children. We profiled gut microbiota using quantitative PCR (qPCR) and evaluated cognitive function using the Corsi block-tapping test (CBT) and the psychomotor vigilance test (PVT) before, during, and after the dietary intervention of 127 school-aged children in northern Thailand. While we found that Sinlek rice (SLR) consumption did not significantly alter the abundance of gut microbiota or the cognitive performance of school-aged children, we did find age to be associated with variations in both the gut microbiota profiles and cognitive outcomes. Gammaproteobacteria was significantly lower in the control and SLR groups during the middle time points of both phases (Weeks 4 and 61), and its abundance was associated with age. Cognitive performance using CBT and PVT were also found to be age-sensitive, as older children outperformed younger children on both of these cognitive assessments. Finally, a multiple factor analysis (MFA) revealed that age and cognitive performance best explain individual variation in this study. Collectively, these findings further describe the influence of host variables on the microbial profiles and cognitive outcomes of school-aged children consuming Sinlek rice in Thailand.

Dietary and lifestyle associations with microbiome diversity.

BACKGROUND: Microbial dysbiosis has been closely linked with colorectal cancer development. However, data is limited regarding the relationship of the mucosal microbiome, adenomatous polyps and dietary habits. Understanding these associations may elucidate pathways for risk stratification according to diet. RESULTS: Patients undergoing screening colonoscopy were included in our prospective, single center study and divided into adenoma or no adenoma cohorts. Oral, fecal, and mucosal samples were obtained. Microbial DNA was extracted, and amplicon libraries generated using primers for the 16S rRNA gene V4 region. Patient and dietary information was collected. Of 104 participants, 44% presented with polyps, which were predominantly tubular adenomas (87%). Adenoma formation and multiple patient dietary and lifestyle characteristics were associated with mucosal microbiome diversity. Lifestyle factors included age, body mass index, adenoma number, and dietary consumption of red meats, processed meats, vegetables, fruit, grain, fermented foods and alcohol. CONCLUSION: In this study we showed associations between dietary habits, adenoma formation and the mucosal microbiome. These early findings suggest that ongoing research into diet modification may help reduce adenoma formation and subsequently the development of CRC.

Age and micronutrient effects on the microbiome in a mouse model of zinc depletion and supplementation.

Older adult populations are at risk for zinc deficiency, which may predispose them to immune dysfunction and age-related chronic inflammation that drives myriad diseases and disorders. Recent work also implicates the gut microbiome in the onset and severity of age-related inflammation, indicating that dietary zinc status and the gut microbiome may interact to impact age-related host immunity. We hypothesize that age-related alterations in the gut microbiome contribute to the demonstrated zinc deficits in host zinc levels and increased inflammation. We tested this hypothesis with a multifactor two-part study design in a C57BL/6 mouse model. The two studies included young (2 month old) and aged (24 month old) mice fed either (1) a zinc adequate or zinc supplemented diet, or (2) a zinc adequate or marginal zinc deficient diet, respectively. Overall microbiome composition did not significantly change with zinc status; beta diversity was driven almost exclusively by age effects. Microbiome differences due to age are evident at all taxonomic levels, with more than half of all taxonomic units significantly different. Furthermore, we found 150 out of 186 genera were significantly different between the two age groups, with Bacteriodes and Parabacteroides being the primary taxa of young and old mice, respectively. These data suggest that modulating individual micronutrient concentrations does not lead to comprehensive microbiome shifts, but rather affects specific components of the gut microbiome. However, a phylogenetic agglomeration technique (ClaaTU) revealed phylogenetic clades that respond to modulation of dietary zinc status and inflammation state in an age-dependent manner. Collectively, these results suggest that a complex interplay exists between host age, gut microbiome composition, and dietary zinc status.