The oral microbiome is associated with HPA axis response to a psychosocial stressor.

Intense psychosocial stress during early life has a detrimental effect on health-disease balance in later life. Simultaneously, despite its sensitivity to stress, the developing microbiome contributes to long-term health. Following stress exposure, HPA-axis activation regulates the "fight or flight" response with the release of glucose and cortisol. Here, we investigated the interaction between the oral microbiome and the stress response. We used a cohort of 115 adults, mean age 24, who either experienced institutionalisation and adoption (n = 40) or were non-adopted controls (n = 75). Glucose and cortisol measurements were taken from participants following an extended socially evaluated cold pressor test (seCPT) at multiple time points. The cohort´s oral microbiome was profiled via 16S-V4 sequencing on microbial DNA from saliva and buccal samples. Using mixed-effect linear regressions, we identified 12 genera that exhibited an interaction with host's cortisol-glucose response to stress, strongly influencing intensity and clearance of cortisol and glucose following stress exposure. Particularly, the identified taxa influenced the glucose and cortisol release profiles and kinetics following seCPT exposure. In conclusion, our study provided evidence for the oral microbiome modifying the effect of stress on the HPA-axis and human metabolism, as shown in glucose-cortisol time series data.

Lateral root enriched Massilia associated with plant flowering in maize.

BACKGROUND: Beneficial associations between plants and soil microorganisms are critical for crop fitness and resilience. However, it remains obscure how microorganisms are assembled across different root compartments and to what extent such recruited microbiomes determine crop performance. Here, we surveyed the root transcriptome and the root and rhizosphere microbiome via RNA sequencing and full-length (V1-V9) 16S rRNA gene sequencing from genetically distinct monogenic root mutants of maize (Zea mays L.) under different nutrient-limiting conditions. RESULTS: Overall transcriptome and microbiome display a clear assembly pattern across the compartments, i.e., from the soil through the rhizosphere to the root tissues. Co-variation analysis identified that genotype dominated the effect on the microbial community and gene expression over the nutrient stress conditions. Integrated transcriptomic and microbial analyses demonstrated that mutations affecting lateral root development had the largest effect on host gene expression and microbiome assembly, as compared to mutations affecting other root types. Cooccurrence and trans-kingdom network association analysis demonstrated that the keystone bacterial taxon Massilia (Oxalobacteraceae) is associated with root functional genes involved in flowering time and overall plant biomass. We further observed that the developmental stage drives the differentiation of the rhizosphere microbial assembly, especially the associations of the keystone bacteria Massilia with functional genes in reproduction. Taking advantage of microbial inoculation experiments using a maize early flowering mutant, we confirmed that Massilia-driven maize growth promotion indeed depends on flowering time. CONCLUSION: We conclude that specific microbiota supporting lateral root formation could enhance crop performance by mediating functional gene expression underlying plant flowering time in maize. Video Abstract.

The gut-brain axis in individuals with alcohol use disorder: An exploratory study of associations among clinical symptoms, brain morphometry, and the gut microbiome.

BACKGROUND: Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut-brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment-seeking individuals with AUD. METHODS: We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut-brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features. RESULTS: Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia, Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri. CONCLUSIONS: We identified gut microbiome features associated with MRI morphometry and AUD-associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut-brain communication and how signaling may be altered in patients with AUD.

Weight, habitual fibre intake, and microbiome composition predict tolerance to fructan supplementation.

Fructans are commonly used as dietary fibre supplements for their ability to promote the growth of beneficial gut microbes. However, fructan consumption has been associated with various dosage-dependent side effects. We characterised side effects in an exploratory analysis of a randomised trial in healthy adults (n = 40) who consumed 18 g/day inulin or placebo. We found that individuals weighing more or habitually consuming higher fibre exhibited the best tolerance. Furthermore, we identified associations between gut microbiome composition and host tolerance. Specifically, higher levels of Christensenellaceae R-7 group were associated with gastrointestinal discomfort, and a machine-learning-based approach successfully predicted high levels of flatulence, with [Ruminococcus] torques group and (Oscillospiraceae) UCG-002 sp. identified as key predictive taxa. These data reveal trends that can help guide personalised recommendations for initial inulin dosage. Our results support prior ecological findings indicating that fibre supplementation has the greatest impact on individuals whose baseline fibre intake is lowest.

Do Tasmanian devil declines impact ecosystem function?

Tasmanian eucalypt forests are among the most carbon-dense in the world, but projected climate change could destabilize this critical carbon sink. While the impact of abiotic factors on forest ecosystem carbon dynamics have received considerable attention, biotic factors such as the input of animal scat are less understood. Tasmanian devils (Sarcophilus harrisii)-an osteophageous scavenger that can ingest and solubilize nutrients locked in bone material-may subsidize plant and microbial productivity by concentrating bioavailable nutrients (e.g., nitrogen and phosphorus) in scat latrines. However, dramatic declines in devil population densities, driven by the spread of a transmissible cancer, may have underappreciated consequences for soil organic carbon (SOC) storage and forest productivity by altering nutrient cycling. Here, we fuse experimental data and modeling to quantify and predict future changes to forest productivity and SOC under various climate and scat-quality futures. We find that devil scat significantly increases concentrations of nitrogen, ammonium, phosphorus, and phosphate in the soil and shifts soil microbial communities toward those dominated by r-selected (e.g., fast-growing) phyla. Further, under expected increases in temperature and changes in precipitation, devil scat inputs are projected to increase above- and below-ground net primary productivity and microbial biomass carbon through 2100. In contrast, when devil scat is replaced by lower-quality scat (e.g., from non-osteophageous scavengers and herbivores), forest carbon pools are likely to increase more slowly, or in some cases, decline. Together, our results suggest often overlooked biotic factors will interact with climate change to drive current and future carbon pool dynamics in Tasmanian forests.

Gut microbiome signatures associated with type 2 diabetes in obesity in Mongolia.

Mongolian people possess a unique dietary habit characterized by high consumption of meat and dairy products and fewer vegetables, resulting in the highest obesity rate in East Asia. Although obesity is a known cause of type 2 diabetes (T2D), the T2D rate is moderate in this population; this is known as the "Mongolian paradox." Since the gut microbiota plays a key role in energy and metabolic homeostasis as an interface between food and body, we investigated gut microbial factors involved in the prevention of the co-occurrence of T2D with obesity in Mongolians. We compared the gut microbiome and metabolome of Mongolian adults with obesity with T2D (DO: n = 31) or without T2D (NDO: n = 35). Dysbiotic signatures were found in the gut microbiome of the DO group; lower levels of Faecalibacterium and Anaerostipes which are known as short-chain fatty acid (SCFA) producers and higher levels of Methanobrevibacter, Desulfovibrio, and Solobacterium which are known to be associated with certain diseases. On the other hand, the NDO group exhibited a higher level of fecal SCFA concentration, particularly acetate. This is consistent with the results of the whole shotgun metagenomic analysis, which revealed a higher relative abundance of SCFA biosynthesis-related genes encoded largely by Anaerostipes hadrus in the NDO group. Multiple logistic regression analysis including host demographic parameters indicated that acetate had the highest negative contribution to the onset of T2D. These findings suggest that SCFAs produced by the gut microbial community participate in preventing the development of T2D in obesity in Mongolians.

High salt diet alleviates disease severity in native experimental autoimmune uveitis.

Background: Recent studies reported a link between high salt diet (HSD) and clinical exacerbation in mouse models of autoimmune diseases, mainly through the induction of pathogenic Th17 cells and/or HSD-induced dysbiosis. However, the topic remains controversial and not fully understood. Purpose: In this study, we investigated the effects of HSD on the development of experimental autoimmune uveitis (EAU) in C57BL/6J mice. Methods and results: Unexpectedly, our data showed a significant attenuating effect of HSD on disease severity of native EAU, induced by direct immunization with IRBP peptide. That said, HSD had no effect on EAU disease severity induced by adoptive transfer of semi-purified auto-reactive IRBP-specific T lymphocytes. Accordingly, HSD did not affect IRBP-specific systemic afferent immune response as attested by no HSD-linked changes in T lymphocytes proliferation, cytokine production and Treg proportion. Gut microbiota analysis from cecal samples in naïve and EAU mice demonstrated that HSD affected differentially α-diversity between groups, whereas ß-diversity was significantly modified in all groups. Unknown Tannerellaceae was the only taxon associated to HSD exposure in all treatment groups. Interestingly, a significantly higher abundance of unknown Gastranaerophilales, with potential anti-inflammatory properties, appeared in HSD-fed native EAU mice, only. Discussion: In conclusion, our study suggests a possible impact of HSD on gut microbiota composition and consequently on development and clinical severity of EAU. Further studies are required to investigate the potential beneficial role of Gastranaerophilales in EAU.

The growth-promoting and disease-suppressing mechanisms of Trichoderma inoculation on peanut seedlings.

Trichoderma spp. is known for its ability to enhance plant growth and suppress disease, but the mechanisms for its interaction with host plants and pathogens remain unclear. This study investigated the transcriptomics and metabolomics of peanut plants (Arachis hypogaea L.) inoculated with Trichoderma harzianum QT20045, in the absence and presence of the stem rot pathogen Sclerotium rolfsii JN3011. Under the condition without pathogen stress, the peanut seedlings inoculated with QT20045 showed improved root length and plant weight, increased indole acetic acid (IAA) production, and reduced ethylene level, with more active 1-aminocyclopropane-1-carboxylate acid (ACC) synthase (ACS) and ACC oxidase (ACO), compared with the non-inoculated control. Under the pathogen stress, the biocontrol efficacy of QT20045 against S. rolfsii was 78.51%, with a similar effect on plant growth, and IAA and ethylene metabolisms to the condition with no biotic stress. Transcriptomic analysis of peanut root revealed that Trichoderma inoculation upregulated the expression of certain genes in the IAA family but downregulated the genes in the ACO family (AhACO1 and AhACO) and ACS family (AhACS3 and AhACS1) consistently in the absence and presence of pathogens. During pathogen stress, QT20045 inoculation leads to the downregulation of the genes in the pectinesterase family to keep the host plant's cell wall stable, along with upregulation of the AhSUMM2 gene to activate plant defense responses. In vitro antagonistic test confirmed that QT20045 suppressed S. rolfsii growth through mechanisms of mycelial entanglement, papillary protrusions, and decomposition. Our findings highlight that Trichoderma inoculation is a promising tool for sustainable agriculture, offering multiple benefits from pathogen control to enhanced plant growth and soil health.

Soil pH, developmental stages and geographical origin differently influence the root metabolomic diversity and root-related microbial diversity of Echium vulgare from native habitats.

Improved understanding of the complex interaction between plant metabolism, environmental conditions and the plant-associated microbiome requires an interdisciplinary approach: Our hypothesis in our multiomics study posited that several environmental and biotic factors have modulating effects on the microbiome and metabolome of the roots of wild Echium vulgare plants. Furthermore, we postulated reciprocal interactions between the root metabolome and microbiome. We investigated the metabolic content, the genetic variability, and the prokaryotic microbiome in the root systems of wild E. vulgare plants at rosette and flowering stages across six distinct locations. We incorporated the assessment of soil microbiomes and the measurement of selected soil chemical composition factors. Two distinct genetic clusters were determined based on microsatellite analysis without a consistent alignment with the geographical proximity between the locations. The microbial diversity of both the roots of E. vulgare and the surrounding bulk soil exhibited significant divergence across locations, varying soil pH characteristics, and within the identified plant genetic clusters. Notably, acidophilic bacteria were characteristic inhabitants of both soil and roots under acidic soil conditions, emphasizing the close interconnectedness between these compartments. The metabolome of E. vulgare significantly differed between root samples from different developmental stages, geographical locations, and soil pH levels. The developmental stage was the dominant driver of metabolome changes, with significantly higher concentrations of sugars, pyrrolizidine alkaloids, and some of their precursors in rosette stage plant roots. Our study featured the complex dynamics between soil pH, plant development, geographical locations, plant genetics, plant metabolome and microbiome, shedding light on existing knowledge gaps.

A seasonal study on the microbiomes of Diploid vs. Triploid eastern oysters and their denitrification potential.

Oyster reefs are hotspots of denitrification mediated removal of dissolved nitrogen (N), however, information on their denitrifier microbiota is scarce. Furthermore, in oyster aquaculture, triploids are often preferred over diploids, yet again, microbiome differences between oyster ploidies are unknown. To address these knowledge gaps, farmed diploid and triploid oysters were collected over an annual growth cycle and analyzed using shotgun metagenomics and quantitative microbial elemental cycling (QMEC) techniques. Regardless of ploidy, Psychrobacter genus was abundant, with positive correlations found for genes of central metabolism, DNA metabolism, and carbohydrate metabolism. MAGs (metagenome-assembled genomes) yielded multiple Psychrobacter genomes harboring norB, narH, narI, and nirK denitrification genes, indicating their functional relevance within the eastern oysters. QMEC analysis indicated the predominance of carbon (C) and nitrogen (N) cycling genes, with no discernable patterns between ploidies. Among the N-cycling genes, the nosZII clade was overrepresented, suggesting its role in the eastern oyster's N removal processes.

How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation.

The gut microbiome has come to prominence across research disciplines, due to its influence on major biological systems within humans. Recently, a relationship between the gut microbiome and hematopoietic system has been identified and coined the gut-bone marrow axis. It is well established that the hematopoietic system and gut microbiome separately alter with age; however, the relationship between these changes and how these systems influence each other demands investigation. Since the hematopoietic system produces immune cells that help govern commensal bacteria, it is important to identify how the microbiome interacts with hematopoietic stem cells (HSCs). The gut microbiota has been shown to influence the development and outcomes of hematologic disorders, suggesting dysbiosis may influence the maintenance of HSCs with age. Short chain fatty acids (SCFAs), lactate, iron availability, tryptophan metabolites, bacterial extracellular vesicles, microbe associated molecular patterns (MAMPs), and toll-like receptor (TLR) signalling have been proposed as key mediators of communication across the gut-bone marrow axis and will be reviewed in this article within the context of aging.

Defined synthetic microbial communities colonize and benefit field-grown sorghum.

The rhizosphere constitutes a dynamic interface between plant hosts and their associated microbial communities. Despite the acknowledged potential for enhancing plant fitness by manipulating the rhizosphere, the engineering of the rhizosphere microbiome through inoculation has posed significant challenges. These challenges are thought to arise from the competitive microbial ecosystem where introduced microbes must survive, and the absence of adaptation to the specific metabolic and environmental demands of the rhizosphere. Here, we engineered a synthetic rhizosphere community (SRC1) with the anticipation that it would exhibit a selective advantage in colonizing the host Sorghum bicolor, thereby potentially fostering its growth. SRC1 was assembled from bacterial isolates identified either for their potential role in community cohesion through network analysis or for their ability to benefit from host-specific exudate compounds. The growth performance of SRC1 was assessed in vitro on solid media, in planta under gnotobiotic laboratory conditions, and in the field. Our findings reveal that SRC1 cohesion is most robust when cultivated in the presence of the plant host under laboratory conditions, with lineages being lost from the community when grown either in vitro or in a native field setting. We establish that SRC1 effectively promotes the growth of both above- and below-ground plant phenotypes in both laboratory and native field contexts. Furthermore, in laboratory conditions, these growth enhancements correlate with the transcriptional dampening of lignin biosynthesis in the host. Collectively, these results underscore the potential utility of synthetic microbial communities for modulating crop performance in controlled and native environments alike.

Co-exposure to polyethylene fiber and Salmonella enterica serovar Typhimurium alters microbiome and metabolome of in vitro chicken cecal mesocosms.

Humans and animals encounter a summation of exposures during their lifetime (the exposome). In recent years, the scope of the exposome has begun to include microplastics. Microplastics (MPs) have increasingly been found in locations, including in animal gastrointestinal tracts, where there could be an interaction with Salmonella enterica serovar Typhimurium, one of the commonly isolated serovars from processed chicken. However, there is limited knowledge on how gut microbiomes are affected by microplastics and if an effect would be exacerbated by the presence of a pathogen. In this study, we aimed to determine if acute exposure to microplastics in vitro altered the gut microbiome membership and activity. The microbiota response to a 24 h co-exposure to Salmonella enterica serovar Typhimurium and/or low-density polyethylene (PE) microplastics in an in vitro broiler cecal model was determined using 16S rRNA amplicon sequencing (Illumina) and untargeted metabolomics. Community sequencing results indicated that PE fiber with and without S. Typhimurium yielded a lower Firmicutes/Bacteroides ratio compared with other treatment groups, which is associated with poor gut health, and overall had greater changes to the cecal microbial community composition. However, changes in the total metabolome were primarily driven by the presence of S. Typhimurium. Additionally, the co-exposure to PE fiber and S. Typhimurium caused greater cecal microbial community and metabolome changes than either exposure alone. Our results indicate that polymer shape is an important factor in effects resulting from exposure. It also demonstrates that microplastic-pathogen interactions cause metabolic alterations to the chicken cecal microbiome in an in vitro chicken cecal mesocosm. IMPORTANCE: Researching the exposome, a summation of exposure to one's lifespan, will aid in determining the environmental factors that contribute to disease states. There is an emerging concern that microplastic-pathogen interactions in the gastrointestinal tract of broiler chickens may lead to an increase in Salmonella infection across flocks and eventually increased incidence of human salmonellosis cases. In this research article, we elucidated the effects of acute co-exposure to polyethylene microplastics and Salmonella enterica serovar Typhimurium on the ceca microbial community in vitro. Salmonella presence caused strong shifts in the cecal metabolome but not the microbiome. The inverse was true for polyethylene fiber. Polyethylene powder had almost no effect. The co-exposure had worse effects than either alone. This demonstrates that exposure effects to the gut microbial community are contaminant-specific. When combined, the interactions between exposures exacerbate changes to the gut environment, necessitating future experiments studying low-dose chronic exposure effects with in vivo model systems.

Antibiotic treatment induces microbiome dysbiosis and reduction of neuroinflammation following traumatic brain injury in mice.

Background: The gut microbiome is linked to brain pathology in cases of traumatic brain injury (TBI), yet the specific bacteria that are implicated are not well characterized. To address this gap, in this study, we induced traumatic brain injury (TBI) in male C57BL/6J mice using the controlled cortical impact (CCI) injury model. After 35 days, we administered a broad-spectrum antibiotics (ABX) cocktail (ampicillin, gentamicin, metronidazole, vancomycin) through oral gavage for 2 days to diminish existing microbiota. Subsequently, we inflicted a second TBI on the mice and analyzed the neuropathological outcomes five days later. Results: Longitudinal analysis of the microbiome showed significant shifts in the diversity and abundance of bacterial genera during both acute and chronic inflammation. These changes were particularly dramatic following treatment with ABX and after the second TBI. ABX treatment did not affect the production of short-chain fatty acids (SCFA) but did alter intestinal morphology, characterized by reduced villus width and a lower count of goblet cells, suggesting potential negative impacts on intestinal integrity. Nevertheless, diminishing the intestinal microbiome reduced cortical damage, apoptotic cell density, and microglial/macrophage activation in the cortical and thalamic regions of the brain. Conclusions: Our findings suggest that eliminating colonized gut bacteria via broad-spectrum ABX reduces neuroinflammation and enhances neurological outcomes in TBI despite implications to gut health.

Microbiome of two adult tick species and their laboratory-reared offspring shows intra- and inter-species differences.

Tick-borne pathogens are a significant threat to human and animal health. Exposing the microbial composition of ticks elucidates their potential role in transmitting pathogens and causing disease as well as uncovering their potential interaction with the hosting tick. Our study focused on characterizing the tick microbiome of adult females and their lab-reared larval offspring of two prevalent tick species found on dogs in Nigeria [Rhipicephalus sanguineus s.l. tropical lineage (R. linnaei) and Haemaphysalis leachi]. We investigated the relative phyla abundance, the alpha and beta diversities of microbial communities comparing tick species, and different development stages (adults versus larvae). To the best of our knowledge, this is the first analysis on H. leachi microbiome described from West Africa. Our findings revealed a diverse microbiome with significant differences across species and their developmental stages, highlighting the dominance of the Proteobacteria phylum, followed by Firmicutes and Actinobacteriota. In contrast to H. leachi, for R. linnaei we observed significant differences in the alpha and beta diversities of the microbiome of larvae and adult females. Predominant bacterial genera were identified in R. linnaei, particularly Arsenophonus and Coxiella, which showed increased abundance in adult ticks. In H. leachi, other predominant genera were detected, including Sphingomonas, Comamonas, and Williamsia. Our results contribute to the understanding of microbiome dynamics within ticks and offers insights of tick physiology for addressing public health concerns and developing effective strategies for pathogen control.

Green spaces contribute to structural resilience of the gut microbiota in urban mammals.

The gut microbiome of wild animals is subject to various environmental influences, including those associated with human-induced alterations to the environment. We investigated how the gut microbiota of a synurbic rodent species, the striped field mouse (Apodemus agrarius), change in cities of varying sizes, seeking the urban microbiota signature for this species. Fecal samples for analysis were collected from animals living in non-urbanized areas and green spaces of different-sized cities (Poland). Metagenomic 16S rRNA gene sequencing and further bioinformatics analyses were conducted. Significant differences in the composition of gut microbiomes among the studied populations were found. However, the observed changes were dependent on local habitat conditions, without strong evidence of a correlation with the size of the urbanized area. The results suggest that ecological detachment from a more natural, non-urban environment does not automatically lead to the development of an "urban microbiome" model in the studied rodent. The exposure to the natural environment in green spaces may serve as a catalyst for microbiome transformations, providing a previously underestimated contribution to the maintenance of native gut microbial communities in urban mammals.

Urinary microbiome dysbiosis is associated with an inflammatory environment and perturbed fatty acids metabolism in the pathogenesis of bladder cancer.

BACKGROUND: Bladder cancer is a common malignancy with high recurrence rate. Early diagnosis and recurrence surveillance are pivotal to patients' outcomes, which require novel minimal-invasive diagnostic tools. The urinary microbiome is associated with bladder cancer and can be used as biomarkers, but the underlying mechanism is to be fully illustrated and diagnostic performance to be improved. METHODS: A total of 23 treatment-naïve bladder cancer patients and 9 non-cancerous subjects were enrolled into the Before group and Control group. After surgery, 10 patients from the Before group were further assigned into After group. Void mid-stream urine samples were collected and sent for 16S rDNA sequencing, targeted metabolomic profiling, and flow cytometry. Next, correlations were analyzed between microbiota, metabolites, and cytokines. Finally, receiver operating characteristic (ROC) curves of the urinary biomarkers were plotted and compared. RESULTS: Comparing to the Control group, levels of IL-6 (p < 0.01), IL-8 (p < 0.05), and IL-10 (p < 0.05) were remarkably elevated in the Before group. The α diversity of urine microbiome was also significantly higher, with the feature microbiota positively correlated to the level of IL-6 (r = 0.58, p < 0.01). Significant differences in metabolic composition were also observed between the Before and Control groups, with fatty acids and fatty acylcarnitines enriched in the Before group. After tumor resection, cytokine levels and the overall microbiome structure in the After group remained similar to that of the Before group, but fatty acylcarnitines were significantly reduced (p < 0.05). Pathway enrichment analysis revealed beta-oxidation of fatty acids was significantly involved (p < 0.001). ROC curves showed that the biomarker panel of Actinomycetaceae + arachidonic acid + IL-6 had superior diagnostic performance, with sensitivity of 0.94 and specificity of 1.00. CONCLUSIONS: Microbiome dysbiosis, proinflammatory environment and altered fatty acids metabolism are involved in the pathogenesis of bladder cancer, which may throw light on novel noninvasive diagnostic tool development.

Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity.

BACKGROUND: Fecal microbiota transplantation (FMT) is a therapeutic intervention used to treat diseases associated with the gut microbiome. In the human gut microbiome, phages have been implicated in influencing human health, with successful engraftment of donor phages correlated with FMT treatment efficacy. The impact that gastrointestinal phages exert on human health has primarily been connected to their ability to modulate the bacterial communities in the gut. Nonetheless, how FMT affects recipients' phage populations, and in turn, how this influences the gut environment, is not yet fully understood. In this study, we investigated the effects of FMT on the phageome composition of participants within the Gut Bugs Trial (GBT), a double-blind, randomized, placebo-controlled trial that investigated the efficacy of FMT in treating obesity and comorbidities in adolescents. Stool samples collected from donors at the time of treatment and recipients at four time points (i.e., baseline and 6 weeks, 12 weeks, and 26 weeks post-intervention), underwent shotgun metagenomic sequencing. Phage sequences were identified and characterized in silico to examine evidence of phage engraftment and to assess the extent of FMT-induced alterations in the recipients' phageome composition. RESULTS: Donor phages engrafted stably in recipients following FMT, composing a significant proportion of their phageome for the entire course of the study (33.8 ± 1.2% in females and 33.9 ± 3.7% in males). Phage engraftment varied between donors and donor engraftment efficacy was positively correlated with their phageome alpha diversity. FMT caused a shift in recipients' phageome toward the donors' composition and increased phageome alpha diversity and variability over time. CONCLUSIONS: FMT significantly altered recipients' phage and, overall, microbial populations. The increase in microbial diversity and variability is consistent with a shift in microbial population dynamics. This proposes that phages play a critical role in modulating the gut environment and suggests novel approaches to understanding the efficacy of FMT in altering the recipient's microbiome. TRIAL REGISTRATION: The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTR N12615001351505). Trial protocol: the trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.

Dipotassium glycyrrhizate prevents oral dysbiosis caused by Porphyromonas gingivalis in an in vitro saliva-derived polymicrobial biofilm model.

OBJECTIVES: Oral microbiome dysbiosis prevention is important to avoid the onset and progression of periodontal disease. Dipotassium glycyrrhizate (GK2) is a licorice root extract with anti-inflammatory effects, and its associated mechanisms have been well-reported. However, their effects on the oral microbiome have not been investigated. This study aimed to elucidate the effects of GK2 on the oral microbiome using an in vitro polymicrobial biofilm model. METHODS: An in vitro saliva-derived polymicrobial biofilm model was used to evaluate the effects of GK2 on the oral microbiome. One-week anaerobic culture was performed, in which GK2 was added to the medium. Subsequently, microbiome analysis was performed based on the V1-V2 region of the 16S rRNA gene, and pathogenicity indices were assessed. We investigated the effects of GK2 on various bacterial monocultures by evaluating its inhibitory effects on cell growth, based on culture turbidity. RESULTS: GK2 treatment altered the microbiome structure and decreased the relative abundance of periodontal pathogenic bacteria, including Porphyromonas. Moreover, GK2 treatment reduced the DPP4 activity -a pathogenicity index of periodontal disease. Specifically, GK2 exhibited selective antibacterial activity against periodontal pathogenic bacteria. CONCLUSIONS: These findings suggest that GK2 has a selective antibacterial effect against periodontal pathogenic bacteria; thus, preventing oral microbiome dysbiosis. Therefore, GK2 is expected to contribute to periodontal disease prevention by modulating the oral microbiome toward a state with low inflammatory potential, thereby utilizing its anti-inflammatory properties on the host.