Biology subjects

Suda, W.

Publications and source records attributed to Suda, W..

15 recordsLinked to original sources

bioRxiv2026

Maternal progesterone signaling establishes lifelong oral homeostasis

Pregnancy is accompanied by profound endocrine remodeling, yet the mechanisms by which maternal hormonal signals establish long-term tissue homeostasis remain largely unknown. Here we identify maternal progesterone signaling as a developmental cue that establishes lifelong oral homeostasis through a hormone-lipid-microbiome axis. We show that the membrane progesterone receptor mPR{delta} is selectively expressed in the developing and maternal submandibular glands, where it mediates non-genomic progesterone signaling to promote epithelial differentiation by driving the selective mobilization of docosahexaenoic acid (DHA). Loss of this pathway disrupts salivary gland maturation, reshapes the oral microbial ecosystem through the selective expansion of Pasteurellaceae, and causes local inflammation as well as systemic metabolic dysfunction. Mechanistically, antibiotic treatment abolishes these phenotypes, whereas transfer of the oral microbiota recapitulates disease, demonstrating that developmental defects in the host are translated into long-term pathology through the oral microbiome. Remarkably, maternal--but not adult--DHA supplementation restores salivary gland development and microbial homeostasis and prevents adult disease phenotypes, identifying a critical developmental window during which oral homeostasis is durably established. Collectively, these findings reveal a previously unrecognized maternal endocrine mechanism that establishes lifelong host-microbiome homeostasis and identify developmental programming as a fundamental principle linking maternal physiology to adult health. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/743932v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@178cc90org.highwire.dtl.DTLVardef@1be04beorg.highwire.dtl.DTLVardef@29759dorg.highwire.dtl.DTLVardef@1e89994_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2026

Changes in dysbiosis and gene expression in the gut of wharf roach (Ligia Spp.) fed with expanded polystyrene

The East Asian region, known for its high levels of human and fishery activities, experiences serious plastic pollution in the marine environment, especially in seawater and along coastlines. Wharf roaches (Ligia spp.) collected from the coast of western Japan frequently ingest expanded polystyrene (EPS), which is then excreted as microplastic through their feces. However, the impact of EPS exposure and ingestion on the gut microbiome of wharf roaches remains unclear. Thus, this study aimed to investigate the effects of EPS ingestion on the gut microbiota of wharf roaches by examining their gut microbiota and gene expression. The expression levels of more than 400 genes, including those associated with xenobiotic metabolism, and the abundance of gut microbial community were altered. Microbial analysis revealed that at least five archaeal types, two to four bacterial types, three to seven eukaryotic types, and three viral types were involved in a correlation network composed of strong associations. Among them, Haloquadratum, Halalkalicoccus, and Methanospirillum (archaea); Volvox (eukaryote); and Varicellovirus and T4-like viruses showed significantly increased abundance. Furthermore, covariance structure analysis indicated that the viruses and methanogens played key causal roles as characteristic factors related to EPS administration. In conclusion, EPS disrupts the intestinal environment of wharf roaches and serves as a potential material for viral activation and methane production. Building on our previous field study that identified wharf roaches as potential indicators of coastal EPS pollution, this study provides novel insights into the ecological impacts of EPS ingestion and consequences of plastic pollution.

pharmacology and toxicology↗

bioRxiv2026

High-resolution temporal profiling reveals synchronized dynamics of the mouse gut microbiome

The gut microbiome is a highly dynamic ecosystem, yet its temporal organization remains poorly understood because microbiome sampling is typically limited to sparse time points. To overcome this challenge, we developed an automated device to enable continuous fecal sampling from individual mice at minute-to hour-scale resolution. Combining full-length 16S rRNA amplicon sequencing with a limited set of long-read metagenomic references, we economically reconstructed genome- and function-level trajectories at high temporal resolution. Automated hourly sampling over 14 consecutive days enabled phase analysis, revealing collective synchronization of taxa partitioned by carbohydrate utilization strategies between day and night, with microbial taxa and functional genes showing reproducible temporal succession across mice. Perturbations such as cage transfer or antibiotic treatment transiently disrupted this functional synchronization, followed by recovery toward a coherent dynamical state. This system and analytic frameworks will enable us to explore rapid microbiome dynamics in health and disease.

microbiology↗

bioRxiv2025

Leveraging the salivary microbiome profile to stratify REM sleep behavior disorder and synucleinopathies

Few studies have explored noninvasive biomarkers of synucleinopathies, including Parkinsons disease (PD), and rapid-eye-movement behavior disorder (RBD), a prodromal stage for these conditions. Human oral/salivary microbiomes are altered in PD, highlighting their potential role in both PD pathogenesis and diagnosis. We analyzed 249 salivary microbiomes of controls and patients with idiopathic RBD and various synucleinopathies, including two subgroups divided based on the presence of RBD symptoms, through both cross-sectional and longitudinal studies. The microbiome composition was strikingly similar between patients with RBD and early PD exhibiting RBD symptoms. The area under the curve range for distinguishing RBD from controls and each synucleinopathy was 0.85-0.94. We further performed pseudotime trajectory analysis of the microbiome compositional space; populations with low diversity, enriched Streptococcus, and depleted Neisseria exhibited a brief pseudotime transition from RBD to early PD. Our findings suggest that early PD-like salivary dysbiosis manifests during RBD, allowing for the stratification of synucleinopathies through the innovative use of salivary microbiome profiles.

neuroscience↗

bioRxiv2024

Comprehensive non-black box classification of highly correlated ecological time series pairs containing many zeros: the case of gut microbiome of mice

We developed a new data analysis method, named Coexistence-Exclusion-Synchronization- Antisynchronization (CESA), to reveal statistically significant correlations from a set of integer compositional abundance time series of Operational Taxonomic Unit (OTU) data of mouse gut microbiota. First, time series are transformed to 0 (absence) and 1 (presence), and statistical tests are applied to extract significant coexistence and mutual exclusion relationships. Subsequently, for all pairs, the difference time series are transformed to +1 (up), 0 (even), and -1 (down), and synchronized and antisynchronized pairs are classified based on statistical tests after carefully removing the effect of spurious correlation caused by changes in compositional shares. We performed a comprehensive classification of all pairs based on the p-values in terms of coexistence and synchronization, including time series data with many zeros, which are difficult to analyze using conventional methods. We found that almost all OTUs (419 out of 420) have significant correlations with at least one OTU in one of the four characteristics: coexisting, exclusive, synchronizing, or antisynchronizing. Considering OTU pairs, about 25% of all possible pairs (22,356 out of 87,990) show a high correlation with the p-values less than 10-5, which is less than the inverse of the total number of pairs. Interaction among phyla are summarized as a network diagram. Author summaryThe gut microbiota ecosystem is often thought to be stable. However, when observed over a long period, there are turnovers in the microbiota, each OTU time series is highly non-stationary, and even species with high overall abundance are often observed to have zero values in some periods. In this study, we developed a comprehensive data analysis method for extracting significant correlations between any pair of OTUs, including OTUs whose observed values contain many zeros or exhibit clear non-stationarity, for which processing methods have not yet been established. We focused on pairwise correlations in terms of coexistence, exclusivity, synchrony, and antisynchrony of increase/decrease, and all combinations of pairs were checked by statistical tests based on the p-values. In order to remove spurious correlations in compositional time series, a new method was introduced to correct the sample sizes for the remaining OTUs, hypothetically assuming a situation in which one OTU was not present. Low abundance OTUs are often overlooked in traditional analyses. However, it becomes evident that all OTUs, including those with low abundance, interact strongly with each other. Additionally, our findings suggest that coexistence and synchrony can be summarized as cooperative relationships, while exclusion and antisynchrony can be summarized as antagonistic relationships. Cooperative interactions are more likely to occur between pairs of OTUs in the same phyla, and antagonistic interactions are more likely to appear between OTUs in different phyla. The time series data analysis method developed in this paper includes no black-box, making it broadly applicable to compositional time series data with integer values.

microbiology↗

bioRxiv2023

Connection between drug-mediated neurotransmission and salivary microbiome

Salivary microbiome alterations associated with cognitive function have been reported in patients with neurodegenerative diseases1-3. Gut microorganisms can modulate therapeutic efficacy via drug metabolism4-7. Additionally, several drugs against diabetes and inflammatory bowel disease can lead to microbial dysbiosis8-10. However, the effect of central nervous system (CNS) drug use on the microbiome remains unknown. Here, we show that the usage of anti-dementia drugs, including donepezil and memantine, more largely affects the salivary microbiome composition than the gut microbiome composition. We observed salivary microbiome diversity reduction in patients with neurodegenerative diseases who received N-methyl-D-aspartate receptor inhibitor drugs. Furthermore, the use of acetylcholine-modulating drugs contributed to the salivary microbiome composition, suggesting that the salivary microbiome responds to changes in CNS drug-induced cerebral acetylcholine and glutamate levels. Multivariate analysis adjusted with or without the use of anti-dementia drugs demonstrated that the difference in the salivary microbiome correlated with cognitive function. We show the unique salivary microbiome structure of CNS drug users, suggesting the possibility of monitoring pharmacokinetics using the salivary microbiome. Our results also provide evidence of the presence of the microbiome-oral-brain axis and will accelerate the elucidation of the interplay between the salivary microbiome and neurodegeneration.

microbiology↗

bioRxiv2023

Dimension reduction of microbiome data linked Bifidobacterium to allergic rhinitis

Dimension reduction has been used to visualise the distribution of multidimensional microbiome data, but the composite variables calculated by the dimension reduction methods have not been widely used to investigate the relationship of the human gut microbiome with lifestyle and disease. In the present study, we applied several dimension reduction methods, including principal component analysis (PCA), principal coordinate analysis (PCoA), non-metric multidimensional scaling (NMDS), and non-negative matrix factorization (NMF), to a microbiome dataset from 186 subjects with symptoms of AR and 106 controls. All the dimension reduction methods supported that the enterotype clusters were overlapped in the dimension reduction plots, and that the distribution of microbial data points appeared to be continuous rather than discrete. Comparison of the composite variables calculated from the different dimension reduction methods showed that the characteristics of the composite variables differed between the dimension reduction methods. The second composite variable calculated from PCoA was significantly associated with the intake of several nutrients, including omega-3 polyunsaturated fatty acids, and the risk of AR. The composite variable was also correlated with the relative abundance of Bifidobacterium, and thus, Bifidobacterium was related to the risk of AR and intake of several nutrients through dimension reduction. Our results highlight the usefulness of the dimension reduction methods for investigating the association of microbial composition with lifestyle and disease in clinical research.

microbiology↗

bioRxiv2023

Dietary fiber induces a fat preference associated with the gut microbiota

Eating behavior is essential to human health. However, whether future eating behavior is subjected to the conditioning of precedent dietary composition is unknown. This study aimed to investigate the effect of dietary fiber consumption on subsequent nutrient-specific food preferences between palatable high-fat and high-sugar diets and explore its correlation with the gut microbiota. C57BL/6NJcl male mice were subjected to a 2-week dietary intervention and fed either a control (n = 6) or inulin (n = 6) diet. Afterwards, all mice were subjected to a 3-day eating behavioral test to self-select a high-fat or a high-sugar diet. The test diet feed intakes were recorded, and the mices fecal samples were analyzed to evaluate the gut microbiota composition. The inulin mice exhibited a preference for a high-fat diet over a high-sugar diet, associated with distinct gut microbiota compositions profiles between the inulin and control mice. The gut microbiota Bacteroides acidifaciens (99.68%), Bacteroides caecemuris (99.37%), and Bacteroides xylanolyticus (92.28%) positively correlated with a preference for fat. Further studies involving fecal microbiota transplantation and eating behavior-related neurotransmitter analyses may clarify the role of gut microbiota on food preferences. Food preferences induced by dietary intervention are a novel observation, and the gut microbiome may be significantly associated with this preference.

microbiology↗

bioRxiv2023

Gastrointestinal transit mathematical model in mice treated with antibiotics

High-resolution fecal pharmacokinetics are crucial for optimizing therapeutic design and evaluating gastrointestinal motility. However, empirical studies with detailed time series data remain limited. This study aims to characterize fecal pharmacokinetics through high-frequency sampling and parallelized fecal concentration quantification, establishing a simple pharmacokinetics model with physiologically interpretable parameters. We quantified vancomycin concentrations in fecal samples collected at a minimum interval of 4 hours from C57BL/6J mice following a single oral administration of either a low (1 mg/mL) or high (20 mg/mL) dose. Fecal concentrations gradually increased and exhibited an exponential decay, leading to the development of a compartmental model with an absorption phase. This simple model accurately fit the experimental data and provided physiological explanations for intra- and inter-individual pharmacokinetics variability. The results suggest that inter-individual differences in pharmacokinetics are attributable to fecal elimination capacity, which may be influenced by drug dosage via changes in gastrointestinal motility. Since the model predicts antibiotic concentrations within the gastrointestinal tract, it can be applied to fundamental studies investigating the effects of antibiotics on the gut microbiome and gastrointestinal motility.

physiology↗

bioRxiv2023

Uncovering plant microbiomes using long-read metagenomic sequencing

The microbiome of plants plays a pivotal role in their growth and health. Despite its importance, many fundamental questions about the microbiome remain largely unanswered, such as the identification of colonizing bacterial species, the genes they carry, and the location of these genes on chromosomes or plasmids. To gain insights into the genetic makeup of the rice leaf microbiome, we performed a metagenomic analysis using long-read sequences, and developed a genomic DNA extraction method that provides relatively intact DNA for long-read sequencing. 1.8 Gb reads were assembled into 26,067 contigs, including 136 circular sequences of less than 1 Mbp, as well as 172 large ([≥] 1 Mbp) sequences, six of which were circularized. Within these contigs, 669 complete 16S rRNA genes were clustered into 166 bacterial species, 130 of which showed low identity to previously defined sequences, suggesting that they represent novel species. The large circular contigs contain novel chromosomes and a megaplasmid, and most of the smaller circular contigs (<1 Mbp) were defined as novel plasmids or bacteriophages. One circular contig represents the complete chromosome of an uncultivated bacterium in the candidate phylum Candidatus Saccharibacteria. Our findings demonstrate the efficacy of long-read-based metagenomics for profiling microbial communities and discovering novel sequences in plant-microbiome studies.

microbiology↗

bioRxiv2022

Lifelong temporal dynamics of the gut microbiome associated with longevity in mice

The temporal changes of the gut microbiome are thought to be critical for understanding its interactions with host aging, but lifelong dynamics within the same individual remain largely unknown. Here we firstly report the high temporal resolution dynamics of gut microbiomes in mice sharing the same genetic background and environment from their birth to natural death, spanning >1,000 days. The 16S rRNA sequencing analysis revealed 9 patterns of OTU temporal dynamics and 38 common "life-core" bacterial species/operational taxonomic units (OTUs) in [≥]80% of all samples across the lifespan of individual mice. The life-core OTUs are largely represented by the phylum Bacteroidota, whereas the transient bacterial group predominantly includes the phylum Firmicutes (Bacillota). Despite the shared genetic background and dietary habits, the gut microbiome structure significantly diversified with age and among individuals. A positive correlation existed between longevity and the microbiome -diversity in middle age (200-500 days) followed by a negative correlation in old age (>700 days), likely influenced by the increase in diversity during the last days of life. The abundance of several "life-core" species also exhibited non-static correlation trends with lifespan. Overall, this research characterized the gut microbiomes based on its persistence over hosts lifetime and suggested a non-static host-microbiome relationship within individual mice.

microbiology↗

bioRxiv2021

Multiple nutritional and gut microbial factors associated with allergic rhinitis: the Hitachi Health Study

Several studies suggest the involvement of dietary habits and gut microbiome in allergic diseases. However, little is known about the nutritional and gut microbial factors associated with the risk of allergic rhinitis (AR). We recruited 186 apparently healthy workers with symptoms of AR and 106 controls at the Hitachi Health Care Center, Japan. The habitual consumption of 42 selected nutrients were examined using the brief-type self-administered diet history questionnaire. Faecal samples were collected and subjected to amplicon sequencing of the 16S ribosomal RNA gene hypervariable regions. Association analysis revealed that four nutrients (retinol, vitamin A, cryptoxanthin, and copper) were negatively associated with AR. Among 40 genera examined, relative abundance of Prevotella and Escherichia were associated with AR. Furthermore, significant statistical interactions were observed between retinol and Prevotella. The age- and sex-adjusted odds of AR were 25-fold lower in subjects with high retinol intake and high Prevotella abundance compared to subjects with low retinol intake and low Prevotella abundance. Our data provide insights into complex interplay between dietary nutrients, gut microbiome, and the development of AR.

microbiology↗

bioRxiv2020

Species-specific assembly of root-associated bacterial microbiota mediated by a combination of plant specialized metabolites

Plant specialized metabolites (PSMs) influence the taxonomic compositions of the root-associated microbiota; however, the underlying molecular mechanisms and evolutionary trajectories remain elusive. Here, we show that the bacterial genus Arthrobacter is predominant in the tobacco endosphere, and that its enrichment is mediated by a combination of two tobacco-specific PSMs, santhopine and nicotine The isolation and whole genome sequencing of a representative set of Arthrobacter strains identified independent genomic features, including but not limited to genes for santhopine and nicotine catabolism, which are associated with the colonization competence of tobacco roots. Taken together, these data suggest that plant species-specific root microbiota assembly is mediated by bacterial catabolism of a cocktail of PSMs synthesized by the host plant.

microbiology↗

bioRxiv2019

Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis

The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases (IBDs); however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin not only establishes a first-line barrier against pathogens, but also serves as a niche for microbial growth. We hypothesized that dysbiosis may cause abnormal mucin utilization and microbial metabolic dysfunction. To test this hypothesis, we analyzed short-chain fatty acids (SCFAs) and mucin components in the stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohns disease (CD) patients from Japan. The levels of n-butyrate were significantly lower in the stools of both the CD and UC patients than in those of the healthy subjects. Correlation analysis identified 7 bacterial species positively correlated with n-butyrate levels, among which the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans act as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in the colonic lamina propria. Importantly, the availability of mucin-associated O-glycans to the microbiota was significantly reduced in n-butyrate-deficient UC patients. Taken together, our findings highlight the biological significance of the symbiosynthesis pathway in the production of n-butyrate, which maintains gut immune homeostasis.

microbiology↗

bioRxiv2018

Ancient DNA analysis of food remains in human dental calculus from the Edo period, Japan

Objectives: Although there are many methods for reconstructing diets of the past, detailed taxon identification is still challenging, and most plants hardly remain at a site. In this study, we applied DNA metabarcoding to dental calculus of Edo people for the taxonomic identification of food species.\n\nMaterials and Methods: DNA was extracted from 13 human dental calculi from the Unko-in site (18th-19th century) of the Edo period, Japan. Polymerase chain reaction (PCR) and sequencing were performed using a primer set specific to the genus Oryza, because rice (Oryza sativa) was a staple food and this was the only member of this genus present in Japan at that time. DNA metabarcoding targeting plants, animals (meat and fish), and fungi was also carried out to investigate dietary diversity.\n\nResults: We detected amplified products of the genus Oryza from more than half of the samples using PCR and Sanger sequencing. DNA metabarcoding enabled us to identify taxa of plants and fungi, although taxa of animals were not detected, except human.\n\nDiscussion: Most of the plant taxonomic groups are present in Japan and include species consumed as food at that time, as confirmed by historical literature. The other groups featured in the lifestyle of Edo people, such as for medicinal purposes and tobacco. The results indicate that plant DNA analysis from calculus provides information about food diversity and lifestyle habits from the past and can complement other analytical methods such as starch analysis and stable isotope analysis.

molecular biology↗