Multi-Omics Analysis of Gut Microbiota and Host Transcriptomics Reveal Dysregulated Immune Response and Metabolism in Young Adults with Irritable Bowel Syndrome.

The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the associations among gut microbiota and host transcriptomics in young adults with IBS. Stool and peripheral blood samples from 20 IBS subjects and 21 healthy controls (HCs) collected at the baseline visit of an RCT were sequenced to depict the gut microbiota and transcriptomic profiles, respectively. The diversities, composition, and predicted metabolic pathways of gut microbiota significantly differed between IBS subjects and HCs. Nine genera were significantly abundant in IBS stool samples, including Akkermansia, Blautia, Coprococcus, Granulicatella, Holdemania, Oribacterium, Oscillospira, Parabacteroides, and Sutterella. There were 2264 DEGs found between IBS subjects and HCs; 768 were upregulated, and 1496 were downregulated in IBS participants compared with HCs. The enriched gene ontology included the immune system process and immune response. The pathway of antigen processing and presentation (hsa04612) in gut microbiota was also significantly different in the RNA-seq data. Akkermansia, Blautia, Holdemania, and Sutterella were significantly correlated with ANXA2P2 (upregulated, positive correlations), PCSK1N (downregulated, negative correlations), and GLTPD2 (downregulated, negative correlations). This study identified the dysregulated immune response and metabolism in IBS participants revealed by the altered gut microbiota and transcriptomic profiles.

Multivariate log-contrast regression with sub-compositional predictors: Testing the association between preterm infants' gut microbiome and neurobehavioral outcomes.

To link a clinical outcome with compositional predictors in microbiome analysis, the linear log-contrast model is a popular choice, and the inference procedure for assessing the significance of each covariate is also available. However, with the existence of multiple potentially interrelated outcomes and the information of the taxonomic hierarchy of bacteria, a multivariate analysis method that considers the group structure of compositional covariates and an accompanying group inference method are still lacking. Motivated by a study for identifying the microbes in the gut microbiome of preterm infants that impact their later neurobehavioral outcomes, we formulate a constrained integrative multi-view regression. The neurobehavioral scores form multivariate responses, the log-transformed sub-compositional microbiome data form multi-view feature matrices, and a set of linear constraints on their corresponding sub-coefficient matrices ensures the sub-compositional nature. We assume all the sub-coefficient matrices are possible of low-rank to enable joint selection and inference of sub-compositions/views. We propose a scaled composite nuclear norm penalization approach for model estimation and develop a hypothesis testing procedure through de-biasing to assess the significance of different views. Simulation studies confirm the effectiveness of the proposed procedure. We apply the method to the preterm infant study, and the identified microbes are mostly consistent with existing studies and biological understandings.

Candida albicans induces mucosal bacterial dysbiosis that promotes invasive infection.

Infectious complications are a common cause of morbidity and mortality in cancer patients undergoing chemotherapy due to increased risk of oral and gastrointestinal candidiasis, candidemia and septicemia. Interactions between C. albicans and endogenous mucosal bacteria are important in understanding the mechanisms of invasive infection. We published a mouse intravenous chemotherapy model that recapitulates oral and intestinal mucositis, and myelosuppression in patients receiving 5-fluorouracil. We used this model to study the influence of C. albicans on the mucosal bacterial microbiome and compared global community changes in the oral and intestinal mucosa of the same mice. We validated 16S rRNA gene sequencing data by qPCR, in situ hybridization and culture approaches. Mice receiving both 5Fu and C. albicans had an endogenous bacterial overgrowth on the oral but not the small intestinal mucosa. C. albicans infection was associated with loss of mucosal bacterial diversity in both sites with indigenous Stenotrophomonas, Alphaproteobacteria and Enterococcus species dominating the small intestinal, and Enterococcus species dominating the oral mucosa. Both immunosuppression and Candida infection contributed to changes in the oral microbiota. Enterococci isolated from mice with oropharyngeal candidiasis were implicated in degrading the epithelial junction protein E-cadherin and increasing the permeability of the oral epithelial barrier in vitro. Importantly, depletion of these organisms with antibiotics in vivo attenuated oral mucosal E-cadherin degradation and C. albicans invasion without affecting fungal burdens, indicating that bacterial community changes represent overt dysbiosis. Our studies demonstrate a complex interaction between C. albicans, the resident mucosal bacterial microbiota and the host environment in pathogenesis. We shed significant new light on the role of C. albicans in shaping resident bacterial communities and driving mucosal dysbiosis.

Red Fluorescence of European Hedgehog (Erinaceus europaeus) Spines Results from Free-Base Porphyrins of Potential Microbial Origin.

Bioluminescence has been recognized as an important means for inter- and intra-species communication. A growing number of reports of red fluorescence occurring in keratinaceous materials have become available. The fluorophore(s) in these cases were shown to be, or suspected to be, free base porphyrins. The red fluorescence found in the downs of bustards was associated with inter-species signaling in mate selection. First reported in 1925, we confirm that spines of the European hedgehog (Erinaceus europaeus) when irradiated with UV (365-395 nm) light display red fluorescence localized in the light-colored sections of their proximal ends. Using reflectance fluorescence spectroscopy, we confirmed that the fluorophores responsible for the emission are free-base porphyrins, as suspected in the original report. Base-induced degradation of the spine matrix and subsequent HPLC, UV-vis, and ESI+ mass spectrometry analysis revealed the presence of a mixture of coproporphyrin III and uroporphyrin III as predominant porphyrins and a minor fraction of protoporphyrin IX. Investigation of the spine microbiome uncovered the abundant presence of bacteria known to secrete and/or interconvert porphyrins and that are not present on the non-fluorescing quills of the North American porcupine (Erethizon dorsatum). Given this circumstantial evidence, we propose the porphyrins could originate from commensal bacteria. Furthermore, we hypothesize that the fluorescence may be incidental and of no biological function for the hedgehog.

Multi-Omics Analysis on Neurodevelopment in Preterm Neonates: A Protocol Paper.

BACKGROUND: The gut microbiome is an important determinant of health and disease in preterm infants. OBJECTIVES: The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants. METHODS: This prospective, longitudinal study planned to recruit 160 preterm infants born <32 weeks gestational age or weighing <1,500 g and admitted to one of two Level III/IV neonatal intensive care units. During the neonatal intensive care unit period, the primary measures included events of early life pain/stress, gut microbiome, host genetic variations, and neurobehavioral assessment. During follow-up visits, gut microbiome; pain sensitivity; and medical, growth, and developmental outcomes at 4, 8-12, and 18-24 months corrected age were measured. DISCUSSION: As of February 14, 2020, 214 preterm infants have been recruited. We hypothesize that infants who experience greater levels of pain/stress will have altered gut microbiome, including potential adverse outcomes such as necrotizing enterocolitis and host genetic variations, feeding intolerance, and/or neurodevelopmental impairments. These will differ from the intestinal microbiome of preterm infants who do not develop these adverse outcomes. To test this hypothesis, we will determine how alterations in the intestinal microbiome affect the risk of developing necrotizing enterocolitis, feeding intolerance, and neurodevelopmental impairments in preterm infants. In addition, we will examine the interaction between the intestinal microbiome and host genetics in the regulation of intestinal health and neurodevelopmental outcomes.

Fecal Microbiomes in Premature Infants With and Without Parenteral Nutrition-Associated Cholestasis.

INTRODUCTION: Premature infants often require parenteral nutrition (PN) until they reach enteral autonomy which puts them at risk of developing PN-associated cholestasis (PNAC). We sought to compare longitudinal changes in fecal microbiomes of premature infants who developed PNAC versus those who did not despite being on similar PN doses. METHODS: Stool samples from premature infants (gestational age <30 weeks) who developed direct bilirubin ≥1.5 mg/dL while receiving PN were classified as precholestasis, cholestasis, or postcholestasis based on bilirubin levels at the time of sample acquisition and were compared to matched control groups 1, 2, and 3, respectively. RESULTS: A total of 102 fecal samples from 8 cases and 10 controls were analyzed. Precholestasis samples were more abundant in phylum Firmicutes and genus Staphylococcus, whereas control 1 was more abundant in phylum Proteobacteria and genus Escherichia-Shigella. Nonmetric multidimensional scaling ordination plots based on the taxonomic composition of early fecal samples revealed significant separation between cases and controls. On indicator species analysis, genus Bacilli was more prevalent in samples from the precholestasis group, whereas genus Escherichia-Shigella was more prevalent in control 1. With feeding advances, weaning of PN and resolution of PNAC, most differences in microbiota resolved with the exception of control 3 group being more diverse compared to the postcholestasis group. CONCLUSIONS: Premature neonates who develop PNAC, compared to those who do not, show significantly different fecal microbiomes preceding the biochemical detection of cholestasis.

Early-life antibiotics attenuate regulatory T cell generation and increase the severity of murine house dust mite-induced asthma.

INTRODUCTION: Early-life exposure to antibiotics (ABX) has been linked to increases in asthma severity and prevalence in both children and laboratory animals. We explored the immunologic mechanisms behind this association using a mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure. METHODS: Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced. Airway cell counts and differentials; serum immunoglobulin E (IgE); pulmonary function; lung histopathology; pulmonary regulatory T cells (Tregs); and the fecal microbiome were characterized following ABX exposure and induction of experimental asthma. RESULTS: Asthma severity was increased in mice exposed to ABX, including: airway eosinophilia, airway hyper-reactivity, serum HDM-specific IgE, and lung histopathology. ABX treatment led to sharp reduction in fecal microbiome diversity, including the loss of pro-regulatory organisms such as Lachnospira. Pulmonary Tregs were reduced with ABX treatment, and this reduction was directly proportional to diminished microbiome diversity. CONCLUSION: Intermittent exposure to ABX early in life worsened the severity of experimental asthma and reduced pulmonary Tregs; the latter change correlated with decreased microbiome diversity. These data may suggest targets for immunologic or probiotic therapy to counteract the harmful effects of childhood ABX.

Influence of Feeding Type on Gut Microbiome Development in Hospitalized Preterm Infants.

BACKGROUND: Premature infants have a high risk for dysbiosis of the gut microbiome. Mother's own milk (MOM) has been found to favorably alter gut microbiome composition in infants born at term. Evidence about the influence of feeding type on gut microbial colonization of preterm infants is limited. OBJECTIVE: The purpose of this study was to explore the effect of feeding types on gut microbial colonization of preterm infants in the neonatal intensive care unit. METHODS: Thirty-three stable preterm infants were recruited at birth and followed up for the first 30 days of life. Daily feeding information was used to classify infants into six groups (MOM, human donor milk [HDM], Formula, MOM + HDM, MOM + Formula, and HDM + Formula) during postnatal days 0-10, 11-20, and 21-30. Stool samples were collected daily. DNA extracted from stool was used to sequence the 16S rRNA gene. Exploratory data analysis was conducted with a focus on temporal changes of microbial patterns and diversities among infants from different feeding cohorts. Prediction of gut microbial diversity from feeding type was estimated using linear mixed models. RESULTS: Preterm infants fed MOM (at least 70% of the total diet) had highest abundance of Clostridiales, Lactobacillales, and Bacillales compared to infants in other feeding groups, whereas infants fed primarily HDM or formula had a high abundance of Enterobacteriales compared to infants fed MOM. After controlling for gender, postnatal age, weight, and birth gestational age, the diversity of gut microbiome increased over time and was constantly higher in infants fed MOM relative to infants with other feeding types (p < .01). DISCUSSION: MOM benefits gut microbiome development of preterm infants, including balanced microbial community pattern and increased microbial diversity in early life.

Detection and analysis of elusive members of a novel and diverse archaeal community within a thermal spring streamer consortium.

Recent metagenomic analyses of Yellowstone National Park (YNP) thermal spring communities suggested the presence of minor archaeal populations that simultaneous PCR-based assays using traditional 'universal' 16S rRNA gene primers failed to detect. Here we use metagenomics to identify PCR primers effective at detecting elusive members of the Archaea, assess their efficacy, and describe the diverse and novel archaeal community from a circum-neutral thermal spring from the Bechler region of YNP. We determined that a less commonly used PCR primer, Arch349F, captured more diversity in this spring than the widely used A21F primer. A search of the PCR primers against the RDP 16S rRNA gene database indicated that Arch349F also captured the largest percentage of Archaea, including 41 % more than A21F. Pyrosequencing using the Arch349F primer recovered all of the phylotypes present in the clone-based portion of the study and the metagenome of this spring in addition to several other populations of Archaea, some of which are phylogenetically novel. In contrast to the lack of amplification with traditional 16S rRNA gene primers, our comprehensive analyses suggested a diverse archaeal community in the Bechler spring, with implications for recently discovered groups such as the Geoarchaeota and other undescribed archaeal groups.

Effects of astaxanthin on gut microbiota of polo ponies during deconditioning and reconditioning periods.

To determine the effects of astaxanthin (ASTX) supplementation on the equine gut microbiota during a deconditioning-reconditioning cycle, 12 polo ponies were assigned to a control (CON; n = 6) or supplemented (ASTX; 75 mg ASTX daily orally; n = 6) group. All horses underwent a 16-week deconditioning period, with no forced exercise, followed by a 16-week reconditioning program where physical activity gradually increased. Fecal samples were obtained at the beginning of the study (Baseline), after deconditioning (PostDecon), after reconditioning (PostRecon), and 16 weeks after the cessation of ASTX supplementation (Washout). Following DNA extraction from fecal samples, v4 of 16S was amplified and sequenced to determine operational taxonomic unit tables and α-diversity and ß-diversity indices. The total number of observed species was greater at Baseline than PostDecon, PostRecon, and Washout (p ≤ 0.02). A main effect of ASTX (p = 0.01) and timepoint (p = 0.01) was observed on ß-diversity, yet the variability of timepoint was greater (13%) than ASTX (6%), indicating a greater effect of timepoint than ASTX. Deconditioning and reconditioning periods affected the abundance of the Bacteroidetes and Fibrobacteres phyla. Physical activity and ASTX supplementation affect the equine gut microbiome, yet conditioning status may have a greater impact.

The impact of early life experiences and gut microbiota on neurobehavioral development among preterm infants: A longitudinal cohort study.

Objectives: To investigate the impact of early life experiences and gut microbiota on neurobehavioral development among preterm infants during neonatal intensive care unit (NICU) hospitalization. Methods: Preterm infants were followed from the NICU admission until their 28 th postnatal day or until discharge. Daily stool samples, painful/stressful experiences, feeding patterns, and other clinical and demographic data were collected. Gut microbiota was profiled using 16S rRNA sequencing, and operational taxonomic units (OTUs) were selected to predict the neurobehaviors. The neurobehavioral development was assessed by the Neonatal Neurobehavioral Scale (NNNS) at 36 to 38 weeks of post-menstrual age (PMA). Fifty-five infants who had NNNS measurements were included in the sparse log-contrast regression analysis. Results: Preterm infants who experienced high level of pain/stress during the NICU hospitalization that were associated with higher NNNS stress/abstinence scores. Eight operational taxonomic units (OTUs) were identified to be associated with of NNNS subscales after controlling demographic and clinical features, feeding patterns, and painful/stressful experiences. These OTUs, taxa belong to seven genera including Enterobacteriaceae_unclassified, Escherichia-Shigella, Incertae_Sedis, Veillonella, Enterococcus, Clostridium_sensu_stricto_1 , and Streptococcus with five belonging to Firmicutes and two belonging to Proteobacteria phylum. The enriched abundance of Enterobacteriaceae_unclassified (OTU17) and Streptococcus (OTU28) were consistently associated with less optimal neurobehavioral outcomes. The other six OTUs were also associated with infant neurobehavioral responses depending on days at NICU stay. Conclusions: This study explored the dynamic impact of specific OTUs on neurobehavioral development among preterm infants after controlling for early life experiences, i.e., acute and chronic pain/stress, and feeding in the NICU.

The Impact of Early Life Experiences and Gut Microbiota on Neurobehavioral Development in Preterm Infants: A Longitudinal Cohort Study.

OBJECTIVES: The objective of this study is to investigate the impact of early life experiences and gut microbiota on neurobehavioral development in preterm infants during neonatal intensive care unit (NICU) hospitalization. METHODS: Preterm infants were followed from NICU admission until their 28th postnatal day or until discharge. Daily stool samples, painful/stressful experiences, feeding patterns, and other clinical and demographic data were collected. Gut microbiota was profiled using 16S rRNA sequencing, and operational taxonomic units (OTUs) were selected to predict the neurobehaviors. The neurobehavioral development was assessed by the Neonatal Neurobehavioral Scale (NNNS) at 36 to 38 weeks of post-menstrual age (PMA). Fifty-five infants who had NNNS measurements were included in the sparse log-contrast regression analysis. RESULTS: Preterm infants who experienced a high level of pain/stress during the NICU hospitalization had higher NNNS stress/abstinence scores. Eight operational taxonomic units (OTUs) were identified to be associated with NNNS subscales after controlling demographic and clinical features, feeding patterns, and painful/stressful experiences. These OTUs and taxa belonging to seven genera, i.e., Enterobacteriaceae_unclassified, Escherichia-Shigella, Incertae_Sedis, Veillonella, Enterococcus, Clostridium_sensu_stricto_1, and Streptococcus with five belonging to Firmicutes and two belonging to Proteobacteria phylum. The enriched abundance of Enterobacteriaceae_unclassified (OTU17) and Streptococcus (OTU28) were consistently associated with less optimal neurobehavioral outcomes. The other six OTUs were also associated with infant neurobehavioral responses depending on days at NICU stay. CONCLUSIONS: This study explored the dynamic impact of specific OTUs on neurobehavioral development in preterm infants after controlling for early life experiences, i.e., acute and chronic pain/stress and feeding in the NICU. The gut microbiota and acute pain/stressful experiences dynamically impact the neurobehavioral development in preterm infants during their NICU hospitalization.

Sex-specific gut microbiome profiles among preterm infants during the neonatal intensive care hospitalization.

Objectives: The gut microbiota among preterm infants is shaped by sex and feeding types. However, sex-specific weekly patterns of gut microbiome profiles among preterm infants during their neonatal intensive care unit (NICU) hospitalization remain unclear. This study aimed to investigate the effect of sex on the weekly development of preterm neonatal gut microbiota in the first 4 weeks of NICU hospitalization. Methods: This secondary data analysis included 28 preterm neonates with 261 stool samples collected from January 2014 to February 2015 in the Northeastern United States. The 16S rRNA V4 gene regions of the stool samples were sequenced and aligned against the SILVA 132 database by using Mothur 1.42.3. The sex-specific weekly diversity indexes and relative abundance of bacterial taxonomic composition were generated by Mothur and analyzed by R packages. Sex-specific weekly compositional patterns of the gut microbiome and predicted metabolic functions of gut microbiome profiles were compared, respectively. Results: In each week of the NICU hospitalization, preterm females and males had significantly distinguished ß-diversity indices and compositions of gut microbiota. Both females and males had significantly enriched Bifidobacterium, a protection feature, in stool samples collected in the third week compared with those in the second week. The predicted metabolic pathways were significantly different between females and males in the second, third, and fourth week of the NICU hospitalization. Both females and males had significantly abundant pathways. Males consistently had more abundance of "lipopolysaccharide biosynthesis" than females in the second, third, and fourth week. Males also had a significant abundance of "membrane and intracellular structural molecules" and "glycan biosynthesis and metabolism" in the second and third week. Conclusions: Sex shaped the weekly patterns of preterm neonatal gut microbiome profiles during the first 4 weeks of the NICU hospitalization. Further clinical interventions should consider the distinct gut microbiota compositions and predicted functional profiles between female and male preterm neonates.

Trends of fecal calprotectin levels and associations with early life experience in preterm infants.

Background: Preterm infants are at risk for severe infections due to their immature immune systems. Factors such as early life pain/stress experiences and feeding may influence immune activation and maturation of immune systems. However, the underlying mechanism remains unclear. Fecal calprotectin (FCP) is a noninvasive surrogate biomarker of mucosal inflammation in the gastrointestinal tract and has been used in detecting intestinal inflammation in specific pediatric gastrointestinal disorders. Objective: To describe the longitudinal trajectory of FCP levels in preterm infants and investigate the contributing factors that are associated with FCP levels. Design: A longitudinal study design was used. Settings: Preterm infants were recruited from 2 neonatal intensive care units (NICU) of a children's medical center in the North-eastern US. Methods: Preterm infants were followed during their first 4 weeks of NICU hospitalization. Stool samples were collected twice per week to quantify the FCP levels. Cumulative pain/stress experiences and feeding types were measured daily. A linear mixed-effect model was used to examine the associations between FCP levels and demographic and clinical characteristics, cumulative pain/stress, and feeding over time. Results: Forty-nine preterm infants were included in the study. Infants' FCP levels varied largely with a mean of 268.7±261.3 µg/g and increased over time. Preterm infants experienced an average of 7.5±5.0 acute painful procedures and 15.3±20.8 hours of chronic painful procedures per day during their NICU stay. The mean percentage of mother's own milk increased from the first week (57.1±36.5%) to the fourth week (60.7±38.9%) after birth. Elevated FCP concentration was associated with acute and cumulative (chronic) pain/stress levels, mother's own milk, non-White race, and higher severity of illness score. Conclusions: FCP levels were elevated in preterm infants with wide interindividual and intraindividual variations. Cumulative pain/stress during the NICU hospitalization, feeding, race, and health status may influence FCP concentrations in early life that may be associated with inflammatory gut processes.

Passive sampling to scale wastewater surveillance of infectious disease: Lessons learned from COVID-19.

Much of what is known and theorized concerning passive sampling techniques has been developed considering chemical analytes. Yet, historically, biological analytes, such as Salmonella typhi, have been collected from wastewater via passive sampling with Moore swabs. In response to the COVID-19 pandemic, passive sampling is re-emerging as a promising technique to monitor SARS-CoV-2 RNA in wastewater. Method comparisons and disease surveillance using composite, grab, and passive sampling for SARS-CoV-2 RNA detection have found passive sampling with a variety of materials routinely produced qualitative results superior to grab samples and useful for sub-sewershed surveillance of COVID-19. Among individual studies, SARS-CoV-2 RNA concentrations derived from passive samplers demonstrated heterogeneous correlation with concentrations from paired composite samples ranging from weak (R2 = 0.27, 0.31) to moderate (R2 = 0.59) to strong (R2 = 0.76). Among passive sampler materials, electronegative membranes have shown great promise with linear uptake of SARS-CoV-2 RNA observed for exposure durations of 24 to 48 h and in several cases RNA positivity on par with composite samples. Continuing development of passive sampling methods for the surveillance of infectious diseases via diverse forms of fecal waste should focus on optimizing sampler materials for the efficient uptake and recovery of biological analytes, kit-free extraction, and resource-efficient testing methods capable of rapidly producing qualitative or quantitative data. With such refinements passive sampling could prove to be a fundamental tool for scaling wastewater surveillance of infectious disease, especially among the 1.8 billion persons living in low-resource settings served by non-traditional wastewater collection infrastructure.

Oral Enrichment of Streptococcus and its Role in Systemic Inflammation Related to Monocyte Activation in Humans with Cocaine Use Disorder.

Cocaine use is commonly associated with increased chronic systemic inflammation. However, the drivers for cocaine use-mediated systemic inflammation are not fully understood. In the current study, we recruited individuals with cocaine use disorder and healthy individuals who did not use cocaine and collected paired saliva and blood samples. The saliva samples were used to assess the oral microbiome, and the plasma samples were evaluated for 33 cytokines and chemokines. Cocaine users exhibited decreased saliva microbial diversities compared to non-users. Streptococcus was the only increased genus in the saliva from cocaine users, whereas several genera were decreased in cocaine users compared to non-users. Notably, cocaine users exhibited increased plasma levels of several monocyte activation markers, including monocyte chemoattractant protein (MCP)-4, macrophage inflammatory protein (MIP)-3α, macrophage-derived chemokine (MDC), and thymus and activation-regulated chemokine (TARC), all of which were correlated with increased saliva levels of three Streptococcus species. Furthermore, treatment with Streptococcus or its lipoteichoic acid preferentially activated primary human monocytes to produce proinflammatory cytokines and chemokines, such as MIP-3α and TARC, in vitro compared to controls. However, monocytes failed to produce these chemokines after exposure to cocaine or cocaine plus bacteria compared to medium or bacteria alone. This study revealed that chronic cocaine use-associated inflammation in the blood may result from increased oral Streptococcus and its effects on myeloid cell activation, but does not result from cocaine directly.

Altered Gut Microbiota in Irritable Bowel Syndrome and Its Association with Food Components.

The interplay between diet and gut microbiota has gained interest as a potential contributor in pathophysiology of irritable bowel syndrome (IBS). The purpose of this study was to compare food components and gut microbiota patterns between IBS patients and healthy controls (HC) as well as to explore the associations of food components and microbiota profiles. A cross-sectional study was conducted with 80 young adults with IBS and 21 HC recruited. The food frequency questionnaire was used to measure food components. Fecal samples were collected and profiled by 16S rRNA Illumina sequencing. Food components were similar in both IBS and HC groups, except in caffeine consumption. Higher alpha diversity indices and altered gut microbiota were observed in IBS compared to the HC. A negative correlation existed between total observed species and caffeine intake in the HC, and a positive correlation between alpha diversity indices and dietary fiber in the IBS group. Higher alpha diversity and gut microbiota alteration were found in IBS people who consumed caffeine more than 400 mg/d. Moreover, high microbial diversity and alteration of gut microbiota composition in IBS people with high caffeine consumption may be a clue toward the effects of caffeine on the gut microbiome pattern, which warrants further study.

Sex Differences in Gut Microbial Development of Preterm Infant Twins in Early Life: A Longitudinal Analysis.

Infant gut microbiota plays a vital role in immune response, mediates neurobehavioral development and health maintenance. Studies of twins' gut microbiota found that gut microbiota composition and diversity tend to be mature and stable with increasing postnatal age (PNA). Preterm infant gut microbiome shifts dramatically when they were staying in the neonatal intensive care unit (NICU). Compositions and shifting characteristics of gut microbiota among neonatal preterm twins and triplets during their early life are still unknown, which impedes a better understanding of the mechanism underpinning neurobehavioral development and precise intervention/health of preterm neonates. This longitudinal cohort study used a twins/triplets design to investigate the interaction of genetic (e.g., male vs. female) and environmental factors influencing the development of the gut microbiome in early life. We included 39 preterm infants, 12 were Female twins/triplets (Female T/T) including 3 twins pairs and 2 triplets, 12 were male twins (Male T) including 6 twins pairs, and 15 were mixed-sex twins/triplets (Mix T/T) including 6 twins pairs and 1 triplet (8 females and 7 males) during the first four weeks of NICU stay. Weekly gut microbiota patterns between females and males were compared by linear discriminant analysis (LDA) effect size (LEfSe). Metagenomics function of gut microbiota was predicted by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Weekly function (KEGG pathways) differences between females and males were detected by using Statistical Analysis of Metagenomic Profiles (STAMP). Results found that female pairs and male pairs were significantly different in gut microbiome diversity, compositions, and predicted metabolic profiles, importantly, females and males were also significantly dissimilar within their co-twin/triplet pairs of the mixed-sex group, infants of co-twins/triplets shared more similar features than un-related infants from different twins' pair. Future research developing personalized interventions for vulnerable high-risk infants should consider sex, and the interaction of sex and environmental factors.

Protective Effect of Baicalin against Clostridioides difficile Infection in Mice.

This study investigated the prophylactic and therapeutic efficacies of baicalin (BC), a plant-derived flavone glycoside, in reducing the severity of Clostridioides difficile infection (CDI) in a mouse model. In the prophylactic trial, C57BL/6 mice were provided with BC (0, 11, and 22 mg/L in drinking water) from 12 days before C. difficile challenge through the end of the experiment, whereas BC administration started day 1 post challenge in the therapeutic trial. Both challenge and control groups were infected with 106 CFU/mL of hypervirulent C. difficile BAA 1803 spores or sterile PBS, and the clinical and diarrheal scores were recorded for 10 days post challenge. On day 2 post challenge, fecal and tissue samples were collected from mice prophylactically administered with BC for microbiome and histopathologic analysis. Both prophylactic and therapeutic supplementation of BC significantly reduced the severity of colonic lesions and improved CDI clinical progression and outcome compared with control (p < 0.05). Microbiome analysis revealed a significant increase in Gammaproteobacteria and reduction in the abundance of protective microbiota (Firmicutes) in antibiotic-treated and C. difficile-infected mice compared with controls (p < 0.05). However, baicalin supplementation favorably altered the microbiome composition, as revealed by an increased abundance in beneficial bacteria, especially Lachnospiraceae and Akkermansia. Our results warrant follow-up investigations on the use of BC as an adjunct to antibiotic therapy to control gut dysbiosis and reduce C. difficile infection in humans.

Chronic cannabis smoking-enriched oral pathobiont drives behavioral changes, macrophage infiltration, and increases ß-amyloid protein production in the brain.

BACKGROUND: Little is known about chronic cannabis smoking-associated oral microbiome and its effects on central nervous system (CNS) functions. METHODS: In the current study, we have analyzed the saliva microbiome in individuals who chronically smoked cannabis with cannabis use disorder (n = 16) and in non-smoking controls (n = 27). The saliva microbiome was analyzed using microbial 16S rRNA sequencing. To investigate the function of cannabis use-associated oral microbiome, mice were orally inoculated with live Actinomyces meyeri, Actinomyces odontolyticus, or Neisseria elongata twice per week for six months, which mimicked human conditions. FINDINGS: We found that cannabis smoking in humans was associated with oral microbial dysbiosis. The most increased oral bacteria were Streptococcus and Actinomyces genus and the most decreased bacteria were Neisseria genus in chronic cannabis smokers compared to those in non-smokers. Among the distinct species bacteria in cannabis smokers, the enrichment of Actinomyces meyeri was inversely associated with the age of first cannabis smoking. Strikingly, oral exposure of Actinomyces meyeri, an oral pathobiont, but not the other two control bacteria, decreased global activity, increased macrophage infiltration, and increased ß-amyloid 42 protein production in the mouse brains. INTERPRETATION: This is the first study to reveal that long-term oral cannabis exposure is associated oral enrichment of Actinomyces meyeri and its contributions to CNS abnormalities.