Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. DESIGN: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. RESULTS: The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. CONCLUSION: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

Escherichia coli cell factories with altered chromosomal replication scenarios exhibit accelerated growth and rapid biomass production.

BACKGROUND: Generally, bacteria have a circular genome with a single replication origin for each replicon, whereas archaea and eukaryotes can have multiple replication origins in a single chromosome. In Escherichia coli, bidirectional DNA replication is initiated at the origin of replication (oriC) and arrested by the 10 termination sites (terA-J). RESULTS: We constructed E. coli derivatives with additional or ectopic replication origins, which demonstrate the relationship between DNA replication and cell physiology. The cultures of E. coli derivatives with multiple replication origins contained an increased fraction of replicating chromosomes and the cells varied in size. Without the original oriC, E. coli derivatives with double ectopic replication origins manifested impaired growth irrespective of growth conditions and enhanced cell size, and exhibited excessive and asynchronous replication initiation. The generation time of an E. coli strain with three replication origins decreased in a minimal medium supplemented with glucose as the sole carbon source. As well as cell growth, the introduction of additional replication origins promoted increased biomass production. CONCLUSIONS: Balanced cell growth and physiological stability of E. coli under rapid growth condition are affected by changes in the position and number of replication origins. Additionally, we show that, for the first time to our knowledge, the introduction of replication initiation sites to the chromosome promotes cell growth and increases protein production.

Growth retardation of Escherichia coli by artificial increase of intracellular ATP.

Overexpression of phosphoenolpyruvate carboxykinase (PCK) was reported to cause the harboring of higher intracellular ATP concentration in Escherichia coli, accompanied with a slower growth rate. For systematic determination of the relationship between the artificial increase of ATP and growth retardation, PCKWT enzyme was directly evolved in vitro and further overexpressed. The evolved PCK67 showed a 60% greater catalytic efficiency than that of PCKWT. Consequently, the PCK67-overexpressing E. coli showed the highest ATP concentration at the log phase of 1.45 µmol/gcell, with the slowest growth rate of 0.66 h(-1), while the PCKWT-overexpressing cells displayed 1.00 µmol/gcell ATP concentration with the growth rate of 0.84 h(-1) and the control had 0.28 µmol/gcell with 1.03 h(-1). To find a plausible reason, PCK-overexpressing cells in a steady state during chemostat growth were applied to monitor intracellular reactive oxygen species (ROS). Higher amount of intracellular ROS were observed as the ATP levels increased. To confirm the hypothesis of slower growth rate without perturbation of the carbon flux by PCK-overexpression, phototrophic Gloeobacter rhodopsin (GR) was expressed. The GR-expressing strain under illumination harbored 81% more ATP concentration along with 82% higher ROS, with a 54% slower maximum growth rate than the control, while both the GR-expressing strain under dark and dicarboxylate transporter (a control membrane protein)-expressing strain showed a lower ATP and increased ROS, and slower growth rate. Regardless of carbon flux changes, the artificial ATP increase was related to the ROS increase and it was reciprocally correlated to the maximum growth rate. To verify that the accumulated intracellular ROS were responsible for the growth retardation, glutathione was added to the medium to reduce the ROS. As a result, the growth retardation was restored by the addition of 0.1 mM glutathione. Anaerobic culture even enabled the artificial ATP-increased E. coli to grow faster than control. Collectively, it was concluded that artificial ATP increases inhibit the growth of E. coli due to the overproduction of ROS.

Role of gut-derived bacterial lipopolysaccharide and peripheral TLR4 in immobilization stress-induced itch aggravation in a mouse model of atopic dermatitis.

Psychological stress and intestinal leakage are key factors in atopic dermatitis (AD) recurrence and exacerbation. Here, we demonstrate the mechanism underlying bacterial translocation across intestinal epithelial barrier damaged due to stress and further aggravation of trimellitic anhydride (TMA)-induced itch, which remain unclear, in AD mice. Immobilization (IMO) stress exacerbated scratching bouts and colon histological damage, and increased serum corticosterone and lipopolysaccharide (LPS). Orally administered fluorescein isothiocyanate (FITC)-dextran and surgically injected (into the colon) Cy5.5-conjugated LPS were detected in the serum and skin after IMO stress, respectively. The relative abundance of aerobic or facultative anaerobic bacteria was increased in the colon mucus layer, and Lactobacillus murinus, E. coli, Staphylococcus nepalensis, and several strains of Bacillus sp. were isolated from the spleens and mesenteric lymph nodes. Oral antibiotics or intestinal permeability blockers, such as lubiprostone (Lu), 2,4,6-triaminopyrimidine (TAP) and ML-7, inhibited IMO stress-associated itch; however, it was reinduced through intradermal or i.p. injection of LPS without IMO stress. I.p. injection of TAK-242 (resatorvid), a TLR4 inhibitor, abrogated IMO stress-associated itch, which was also confirmed in TLR4-KO mice. IMO stress alone did not cause itch in naïve mice. IMO stress-induced itch aggravation in TMA-treated AD mice might be attributed to the translocation of gut-derived bacterial cells and LPS, which activates peripheral TLR4 signaling.

A Marine Bacterium with Animal-Pathogen-Like Type III Secretion Elicits the Nonhost Hypersensitive Response in a Land Plant.

Active plant immune response involving programmed cell death called the hypersensitive response (HR) is elicited by microbial effectors delivered through the type III secretion system (T3SS). The marine bacterium Hahella chejuensis contains two T3SSs that are similar to those of animal pathogens, but it was able to elicit HR-like cell death in the land plant Nicotiana benthamiana. The cell death was comparable with the transcriptional patterns of H. chejuensis T3SS-1 genes, was mediated by SGT1, a general regulator of plant resistance, and was suppressed by AvrPto1, a type III-secreted effector of a plant pathogen that inhibits HR. Thus, type III-secreted effectors of a marine bacterium are capable of inducing the nonhost HR in a land plant it has never encountered before. This suggests that plants may have evolved to cope with a potential threat posed by alien pathogen effectors. Our work documents an exceptional case of nonhost HR and provides an expanded perspective for studying plant nonhost resistance.

Genome sequence of the agar-degrading marine bacterium Alteromonadaceae sp. strain G7.

Here, we present the high-quality draft genome sequence of the agar-degrading marine gammaproteobacterium Alteromonadaceae sp. strain G7, which was isolated from coastal seawater to be utilized as a bioresource for production of agar-derived biofuels. The 3.91-Mb genome contains a number of genes encoding algal polysaccharide-degrading enzymes such as agarases and sulfatases.

Draft genome sequence of the antifungal-producing plant-benefiting bacterium Burkholderia pyrrocinia CH-67.

Burkholderia pyrrocinia CH-67 was isolated from forest soil as a biocontrol agent to be utilized in agriculture. Here, we report the 8.05-Mb draft genome sequence of this bacterium. Its genome contains genes involved in biosynthesis of secondary metabolites and plant growth promotion, which may contribute to probiotic effects on plants.

Complete genome sequence of the endophytic bacterium Burkholderia sp. strain KJ006.

Endophytes live inside plant tissues without causing any harm and may even benefit plants. Here, we provide the high-quality genome sequence of Burkholderia sp. strain KJ006, an endophytic bacterium of rice with antifungal activity. The 6.6-Mb genome, consisting of three chromosomes and a single plasmid, contains genes related to plant growth promotion or degradation of aromatic compounds.

Complete genome sequence of the probiotic bacterium Bifidobacterium bifidum strain BGN4.

Bifidobacterium bifidum, a common endosymbiotic inhabitant of the human gut, is considered a prominent probiotic microorganism that may promote health. We completely decrypted the 2.2-Mb genome sequence of B. bifidum BGN4, a strain that had been isolated from the fecal sample of a healthy breast-fed infant, and annotated 1,835 coding sequences.

Genome sequence of the leaf-colonizing Bacterium Bacillus sp. strain 5B6, isolated from a cherry tree.

Plant growth-promoting bacteria colonize various habitats, including the phyllosphere. Here, we present the high-quality draft genome sequence of Bacillus sp. strain 5B6, which was isolated from the leaf of a cherry tree. The 3.9-Mb genome uncovers its potential for understanding the nature of leaf colonization as well as antibiosis against plant pathogens.

Genome sequence of an oligohaline hyperthermophilic archaeon, Thermococcus zilligii AN1, isolated from a terrestrial geothermal freshwater spring.

Thermococcus zilligii, a thermophilic anaerobe in freshwater, is useful for physiological research and biotechnological applications. Here we report the high-quality draft genome sequence of T. zilligii AN1(T). The genome contains a number of genes for an immune system and adaptation to a microbial biomass-rich environment as well as hydrogenase genes.

Genome sequence of the hemolytic-uremic syndrome-causing strain Escherichia coli NCCP15647.

Enterohemorrhagic Escherichia coli (EHEC) causes a disease involving diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). Here we present the draft genome sequence of NCCP15647, an EHEC isolate from an HUS patient. Its genome exhibits features of EHEC, such as genes for verotoxins, a type III secretion system, and prophages.

Genome sequence of enterohemorrhagic Escherichia coli NCCP15658.

Enterohemorrhagic Escherichia coli causes severe food-borne disease in the guts of humans and animals. Here, we report the high-quality draft genome sequence of E. coli NCCP15658 isolated from a patient in the Republic of Korea. Its genome size was determined to be 5.46 Mb, and its genomic features, including genes encoding virulence factors, were analyzed.

Genome sequence of the Shiga toxin-producing Escherichia coli strain NCCP15657.

Shiga toxin-producing Escherichia coli causes bloody diarrhea and hemolytic-uremic syndrome and serious outbreaks worldwide. Here, we report the draft genome sequence of E. coli NCCP15657 isolated from a patient. The genome has virulence genes, many in the locus of enterocyte effacement (LEE) island, encoding a metalloprotease, the Shiga toxin, and constituents of type III secretion.

Genome sequence of the plant growth-promoting rhizobacterium Bacillus sp. strain JS.

Volatile and nonvolatile compounds emitted from the plant growth-promoting rhizobacterium Bacillus sp. strain JS enhance the growth of tobacco and lettuce. Here, we report the high-quality genome sequence of this bacterium. Its 4.1-Mb genome reveals a number of genes whose products are possibly involved in promotion of plant growth or antibiosis.

Transcriptional Potential Determines the Adaptability of Escherichia coli Strains with Different Fitness Backgrounds.

Adaptation through the fitness landscape may be influenced by the gene pool or expression network. However, genetic factors that determine the contribution of beneficial mutations during adaptive evolution are poorly understood. In this study, we experimentally evolved wild-type Escherichia coli K-12 MG1655 and its isogenic derivative that has two additional replication origins and shows higher background fitness. During the short time of experimental evolution, the fitness gains of the two E. coli strains with different fitness backgrounds converged. Populational genome sequencing revealed various mutations with different allele frequencies in evolved populations. Several mutations occurred in genes affecting transcriptional regulation (e.g., RNA polymerase subunit, RNase, ppGpp synthetase, and transcription termination/antitermination factor genes). When we introduced mutations into the ancestral E. coli strains, beneficial effects tended to be lower in the ancestor with higher initial fitness. Replication rate analysis showed that the various replication indices do not correlate with the growth rate. Transcriptome profiling showed that gene expression and gene ontology are markedly enriched in populations with lower background fitness after experimental evolution. Further, the degree of transcriptional change was proportional to the fitness gain. Thus, the evolutionary trajectories of bacteria with different fitness backgrounds can be complex and counterintuitive. Notably, transcriptional change is a major contributor to adaptability. IMPORTANCE Predicting the adaptive potential of bacterial populations can be difficult due to their complexity and dynamic environmental conditions. Also, epistatic interaction between mutations affects the adaptive trajectory. Nevertheless, next-generation sequencing sheds light on understanding evolutionary dynamics through high-throughput genome and transcriptome information. Experimental evolution of two E. coli strains with different background fitness showed that the trajectories of fitness gain, which slowed down during the later stages of evolution, became convergent. This suggests that the adaptability of bacteria can be counterintuitive and that predicting the evolutionary path of bacteria can be difficult even in a constant environment. In addition, transcriptional change is associated with fitness gain during the evolutionary process. Thus, the adaptability of cells depends on their intrinsic genetic capacity for a given evolutionary period. This should be considered when genetically engineered bacteria are optimized through adaptive evolution.

Exploring the Differences in the Gut Microbiome in Atopic Dermatitis According to the Presence of Gastrointestinal Symptoms.

(1) Background: Atopic dermatitis (AD) is a multifactorial chronic allergic skin disease. Gastrointestinal (GI) functions have been suggested to be associated with its incidence or severity. As modulators of the gut-skin axis, gut microbes might affect the pathophysiology of AD. (2) Methods: We divided a cohort of patients with AD according to their GI symptoms as follows: AD with epigastric fullness (ADwEF), AD with epigastric rigidity (ADwER), and AD without GI symptoms (ADw/oGI). The gut microbial profiles were analyzed using 16S rRNA amplicon sequencing. (3) Results: The microbiota of the ADwER group showed low diversity indices in richness and evenness and formed a separate cluster to the other groups. In the ADwER group, the proportion of Bacteroides increased, while that of Prevotella decreased; functional pathways related to phosphotransferase systems were not abundant relative to those in the ADw/oGI group. Taken together, patients with AD with GI symptoms have a different microbiome from patients with simple AD. (4) Conclusions: In an exploratory study aimed at evaluating the relationship between AD and GI symptoms, the gut microbiome in patients with AD with GI symptoms differed from that in patients with simple AD, and this result could serve as a basis for further gut-skin axis studies.

Gut microbiota of the young ameliorates physical fitness of the aged in mice.

BACKGROUND: Aging is a natural process that an organism gradually loses its physical fitness and functionality. Great efforts have been made to understand and intervene in this deteriorating process. The gut microbiota affects host physiology, and dysbiosis of the microbial community often underlies the pathogenesis of host disorders. The commensal microbiota also changes with aging; however, the interplay between the microbiota and host aging remains largely unexplored. Here, we systematically examined the ameliorating effects of the gut microbiota derived from the young on the physiology and phenotypes of the aged. RESULTS: As the fecal microbiota was transplanted from young mice at 5 weeks after birth into 12-month-old ones, the thickness of the muscle fiber and grip strength were increased, and the water retention ability of the skin was enhanced with thickened stratum corneum. Muscle thickness was also marginally increased in 25-month-old mice after transferring the gut microbiota from the young. Bacteria enriched in 12-month-old mice that received the young-derived microbiota significantly correlated with the improved host fitness and altered gene expression. In the dermis of these mice, transcription of Dbn1 was most upregulated and DBN1-expressing cells increased twice. Dbn1-heterozygous mice exhibited impaired skin barrier function and hydration. CONCLUSIONS: We revealed that the young-derived gut microbiota rejuvenates the physical fitness of the aged by altering the microbial composition of the gut and gene expression in muscle and skin. Dbn1, for the first time, was found to be induced by the young microbiota and to modulate skin hydration. Our results provide solid evidence that the gut microbiota from the young improves the vitality of the aged. Video Abstract.

Genome information of the cellulolytic soil actinobacterium Isoptericola dokdonensis DS-3 and comparative genomic analysis of the genus Isoptericola.

The actinobacterial group is regarded as a reservoir of biologically active natural products and hydrolytic enzymes with the potential for biomedical and industrial applications. Here, we present the complete genome sequence of Isoptericola dokdonensis DS-3 isolated from soil in Dokdo, small islets in the East Sea of Korea. This actinomycete harbors a large number of genes encoding carbohydrate-degrading enzymes, and its activity to degrade carboxymethyl cellulose into glucose was experimentally evaluated. Since the genus Isoptericola was proposed after reclassification based on phylogenetic analysis, strains of Isoptericola have been continuously isolated from diverse environments and the importance of this genus in the ecosystem has been suggested by recent culturomic or metagenomic studies. The phylogenic relationships of the genus tended to be closer among strains that had been isolated from similar habitats. By analyzing the properties of published genome sequences of seven defined species in the genus, a large number of genes for carbohydrate hydrolysis and utilization, as well as several biosynthetic gene clusters for secondary metabolites, were identified. Genomic information of I. dokdonensis DS-3 together with comparative analysis of the genomes of Isoptericola provides insights into understanding this actinobacterial group with a potential for industrial applications.