During the COVID-19 pandemic, facemasks played a pivotal role in preventing person-person droplet transmission of viral particles. However, prolonged facemask wearing causes skin irritations colloquially referred to as ‘maskne’ (mask + acne), which manifests as acne and contact dermatitis and is mostly caused by pathogenic skin microbes. Previous studies revealed that the putative causal microbes were anaerobic bacteria, but the pathogenesis of facemask-associated skin conditions remains poorly defined. We therefore characterized the role of the facemask-associated skin microbiota in the development of maskne using culture-dependent and -independent methodologies. Metagenomic analysis revealed that the majority of the facemask microbiota were anaerobic bacteria that originated from the skin rather than saliva. Previous work demonstrated direct interaction between pathogenic bacteria and antagonistic strains in the microbiome. We expanded this analysis to include indirect interaction between pathogenic bacteria and other indigenous bacteria classified as either ‘pathogen helper (PH)’ or ‘pathogen inhibitor (PIn)’ strains. In vitro screening of bacteria isolated from facemasks identified both strains that antagonized and promoted pathogen growth. These data were validated using a mouse skin infection model, where we observed attenuation of symptoms following pathogen infection. Moreover, the inhibitor of pathogen helper (IPH) strain, which did not directly attenuate pathogen growth in vitro and in vivo, functioned to suppress symptom development and pathogen growth indirectly through PH inhibitory antibacterial products such as phenyl lactic acid. Taken together, our study is the first to define a mechanism by which indirect microbiota interactions under facemasks can control symptoms of maskne by suppressing a skin pathogen.

Vibrio parahaemolyticus is a major seafood-borne zoonotic pathogen that causes gastroenteritis in humans and acute hepatopancreatic necrosis disease (AHPND) in shrimp. In this study, we isolated and characterized Vibrio phage vB_VpM-pA2SJ1, which infects clinical and AHPND-associated strains of V. parahaemolyticus. The phage genome is a linear dsDNA 51,054 bp in length with a G + C content of 43.7

Background:There is a growing interest in understanding the association between the gut microbiota and inflammatory bowel disease (IBD). Natural compounds, such as Korean Red Ginseng (KRG), show promise for IBD treatment because of their ability to influence gut microbiota. This study explored the effects of KRG on gut microbiota modulation and subsequent intestinal epithelial cell regeneration in an experimental colitis model. Method:Using a mouse model of colitis induced by 2 % dextran sodium sulfate, the study administered 200 or 400 mg/kg/day of KRG to evaluate its biological effects. Colitis symptoms were assessed through body weight, disease activity index, colon length, and histological analysis. The microbial composition in the fecal was determined using 16S rRNA sequencing. To evaluate regeneration signals in the colon, western blotting and immunohistochemistry assays were conducted. Result:Administration of KRG effectively mitigated colitis symptoms in mice, as indicated by histological examination showing alleviated epithelial damage and inflammation, along with increased mucus production. Microbiota analysis showed that KRG significantly altered microbial diversity, favoring beneficial taxa and suppressing harmful taxa. Moreover, ameliorated β-catenin/transcription factor-4 protein expression, a key signal associated with epithelial cell regeneration, was observed in the KRG treated groups, accompanied by improved intestinal linings. Conclusion:These findings suggest that KRG exerts biological effects in colitis by modulating gut microbiota and creating a favorable intestinal environment, thereby reducing regenerative signals. Further research is warranted to elucidate the cellular and molecular mechanisms underlying the interaction of KRG with gut microbiota and pave the way for effective IBD therapies.

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2' -fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2' -fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARSCoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection. (c) 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.

Wearable sensors have evolved significantly, making personalized medicine and real-time disease management possible. However, current digital healthcare is limited to only certain diseases, such as diabetes, due to the lack of mature technologies that can detect small biomolecules. In particular, despite the early detection of chronic kidney disease (CKD) being significant in preventing life-threatening end-stage kidney disease, the development of wearable sensors for CKD monitoring is still in the early stages. In this Perspective, we propose a wearable digital healthcare concept for non-invasive, continuous CKD monitoring, discuss optimal biofluids, biomarkers and bioreceptors to create a wearable CKD sensing platform, and provide insight into potential challenges faced by the technology as well as opportunities.

The human gut microbiota, an intricate ecosystem within the gastrointestinal tract, plays a pivotal role in health and disease. Prebiotics, non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of beneficial microorganisms, have emerged as a key modulator of this complex microbial community. This review article explores the evolution of the prebiotic concept, delineates various types of prebiotics, including fructans, galactooligosaccharides, xylooligosaccharides, chitooligosaccharides, lactulose, resistant starch, and polyphenols, and elucidates their impact on the gut microbiota composition. We delve into the mechanisms through which prebiotics exert their effects, particularly focusing on producing short-chain fatty acids and modulating the gut microbiota towards a health-promoting composition. The implications of prebiotics on human health are extensively reviewed, focusing on conditions such as obesity, inflammatory bowel disease, immune function, and mental health. The review further discusses the emerging concept of synbiotics—combinations of prebiotics and probiotics that synergistically enhance gut health—and highlights the market potential of prebiotics in response to a growing demand for functional foods. By consolidating current knowledge and identifying areas for future research, this review aims to enhance understanding of prebiotics’ role in health and disease, underscoring their importance in maintaining a healthy gut microbiome and overall well-being.

Background: The brain–gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer’s dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients’ fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients’ genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

Clostridium species (phylum Firmicutes) are gram-positive endospore-forming anaerobic bacteria that inhabit diverse environments including animal and human gut, sewage, lake sediments, and paddy soil. Previously, several growth-enhancing Clostridium species isolated from the root and rhizosphere of rice seedlings were classified as plant growth-promoting rhizobacteria (PGPR; Febri et al., 2014; Zeiller et al., 2015); however, some caused disease in potato and kiwifruit (Shabuer et al., 2015; Spigaglia et al., 2020). In agriculture, anaerobic soil disinfestation (ASD), a preplanting soil treatment method that creates anaerobic soil conditions, was conventionally utilized to suppress the growth of soil-borne pathogens such as Ralstonia solanacearum, Fusarium oxysporum, and Verticillium spp. (Momma, 2008; Shennan et al., 2009; Ueki et al., 2018). The determinants of ASD were mainly reported as short-chain fatty acids (SCFAs), such as acetic acid and butyric acid (BA), derived from the metabolic pathways of anaerobic bacteria such as Clostridium spp. (Swilling et al., 2021). However, whether Clostridium spp. closely interact with the plant root under anaerobic conditions remains unclear. Furthermore, little information is available on how the belowground plant–Clostridium interaction contributes to aboveground plant fitness traits such as immunity. In this study, we established a new protocol to isolate anaerobic bacteria from three root compartments, rhizosphere (soil surrounding the root), rhizoplane (root surface), and endosphere (root interior; Ueki et al., 2007; Edwards et al., 2015), in paddy soil, which is an ideal ecological niche for anaerobic bacteria (Liesack et al., 2000). Then, the ability of Clostridium spp. to colonize plant root and improve plant fitness by activating induced systemic resistance (ISR) was evaluated. Lastly, we identified bacterial metabolites that function as ISR determinants, and demonstrated the potential application of BA as a bioprotectant. Collectively, we show that Clostridium spp. elicit ISR and improve plant fitness through root colonization. We compared the microbiome composition of three rice root compartments, rhizosphere, rhizoplane, and endosphere, with that of bulk (unplanted) soil sampled from five different locations in South Korea: Suwon (SW), Cheongju (CJ), Chuncheon (CC), Daegu (DG), and Iksan (IS). A total of 2485 828 sequence reads were generated by 16S rRNA sequencing, with an average of 30 646 reads per sample. The β-diversity indices determined by principal coordinate analysis (PCoA) showed that the microbiome composition of bulk soil was distinct from that of the endosphere and different from those of the rhizospheres and rhizoplane at five sites. Interestingly, the microbiota of rhizosphere and rhizoplane samples were similar in Suwon (SW), Cheongju (CJ), Chuncheon (CC), and Iksan (IS; Fig. 1a). The PCoA results indicated that rhizosphere and rhizoplane samples shared similar microbiota, whereas bulk soil and endosphere had different microbiota. A permutational ANOVA (PERMANOVA; Adonis) analysis showed that the microbiota in each rhizocompartment clustered significantly at all five sites (P = 0.001, for all five sites: SW, CJ, CC, DG, and IS in South Korea). PCoA analysis for the five regions together revealed that the microbiota was clustered by each region rather than by rhizocompartments (Supporting Information Fig. S1). In addition, α-diversity analysis indicates that microbial diversity was highest in bulk soil and rhizosphere, and lowest in endosphere at all five sites (Fig. 1b), indicating that the endosphere is composed of specific microbiota selectively recruited from the bulk soil and rhizosphere (Hardoim et al., 2008; Rodríguez et al., 2020). Analysis of relative abundance at the phylum level revealed that Firmicutes, Proteobacteria, Chloroflexi, Actinobacteria, and Patescibacteria were dominant at all sites (Fig. 1c). The total relative abundance of Firmicutes was up to 62% in the rhizosphere and rhizoplane. Among all three rhizocompartments, rhizosphere showed the highest abundance of Firmicutes at all sites except DG and endosphere showed the lowest abundance of Firmicutes at all sites except SW. Notably, Clostridium was the most dominant Firmicutes genus in the rhizosphere, with a relative abundance of up to 91% (Fig. 1d). Specifically, at the CJ, DG, SW, CC, and IS sites, the abundance of Clostridium spp. was 89%, 73%, 91%, 88%, and 90%, respectively, in the rhizosphere, and 84%, 45%, 63%, 72%, and 77%, respectively, in bulk soil (Fig. 1d). The relative abundance ratio of Clostridium in Firmicutes was significantly higher in the rhizosphere than in bulk soil at all sites. Based on these results, we examined the percentage of reads belonging to Clostridium spp. in each rhizocompartment (Fig. S2a). Interestingly, the percentage of Clostridium read counts followed the order rhizosphere > rhizoplane > endosphere at all sites. The percentages of Clostridium spp. in three rhizocompartments in CC were higher than at other sites and were similar to each other. These results indicate that the environment of the rhizosphere is the most conducive for the survival of Clostridium, whereas that of the endosphere is the most challenging (Fig. S2a). Plant root is known as a gatekeeper that differentiates the bacteria found in rhizosphere and endosphere from those found in bulk soil (Liu et al., 2017). Therefore, we hypothesized that differences in Clostridium ratios between different rhizocompartments could be attributed to differences in oxygen gradient distribution caused by physical barriers, such as the plant root epidermis and endodermis. In addition, oxygen from the atmosphere is transported to the rice root through the aerenchymatous tissue and released into the soil as radial oxygen loss (ROL; Armstrong, 1971). The oxygen introduced into the soil from the root creates an oxygen gradient for each rhizocompartment (Maisch et al., 2019). Compared with the atmosphere, oxygen concentration was 40–60% within the root and 20% on the root surface. Previously, in the rhizosphere of 3-wk-old rice seedlings, at 8 cm below the ground, the oxygen-rich region expanded to 0.4 mm around the root (Revsbech et al., 1999). Based on these results, we hypothesized that the oxygen gradient between the endosphere and bulk soil plays a key role in the distribution of microbiota. To understand the role of oxygen in root microbiome composition (Song et al., 2021), we compared differences in the operational taxonomic units (OTUs) of aerobic and anaerobic bacteria among bulk soil, rhizosphere, rhizoplane, and endosphere. First, we selected OTUs defined as Clostridium (Figs 1e, S2b–e). At CJ and SW, sequences belonging to OTUs 219, 224, 258, 93, 119, and 139 were most abundant in the rhizosphere, followed by rhizoplane and endosphere (Fig. 1e). These results are consistent with the relative abundance and percent of Clostridium present in total read counts, indicating that Clostridium species were enriched in the rhizosphere and were less frequent in the endosphere and bulk soil (Figs 1e, S2a–e). The low abundance of clostridia in bulk soil was presumed to be caused by the lower nutrient availability in soil than in the rhizosphere and rhizoplane, as well as by the lower oxygen level. Interestingly, the aerobic bacteria read counts classified as Bradyrhizobium and Sphingomonas (Surpin & Maier, 1998; Kopejtka et al., 2021) were high in the endosphere, and less high in the rhizosphere (Figs 1f, S3a–c). Subsequently, OTUs of representative aerobic Bacillus spp. were rarely detected at the five sites (Fig. S3d–f). Our results are in agreement with those of a previous study reporting a negative correlation between the relative abundance of Clostridium and that of Bacillus (Hewavitharana et al., 2021). Overall, our results suggest that oxygen is one of the key factors that determines the prevalence of Clostridium in each rhizocompartment. Although Clostridium is known as a representative genus of anaerobic bacteria, its OTUs were also detected in the rice root endosphere, which is rich in oxygen (Maisch et al., 2019). To explain how anaerobic bacteria thrive in an oxygen-rich environment, it was proposed that Clostridium spp. form spores, which can tolerate oxygen (Shen et al., 2019). However, this theory could not be proven because it was difficult to extract DNA from bacterial endospore using the standard protocol for metagenome analysis (Belgrader et al., 1999). Another theory is that specific metabolites produced by Clostridium spp., such as aromatic polyketides, allow bacterial vegetative cells to be active even in an oxygen-rich plant environment (Shabuer et al., 2015). In addition, the composition of the soil microbiome is affected by the gradients of nutrient and defense components released from the plant (Pascale et al., 2020; Kashyap et al., 2021; Kawa & Brady, 2022). Taken together, these results support the possibility of interactions between Clostridium and the host plant at the rhizocompartments. To examine the interaction between Clostridium and rice plants, 89 bacterial strains including 18 strains of Clostridium were isolated from each rhizocompartment as described previously (Ueki et al., 2007; Edwards et al., 2015; Browne et al., 2016), with slight modifications (see the Materials and Methods section; Notes S1; Fig. S4). First, we investigated rice root colonization by C. butyricum strain CC2 as an indicator of the interaction with plant root (Lugtenberg & Kamilova, 2009) because a strong interaction of this strain with plant species has rarely been reported. Fluorescence in situ hybridization analysis revealed that the intensity of light signal gradually increased in the epidermis cell junction of rice root from 3 to 7 d post-inoculation (dpi; Fig. S5; Video S1). Azospirillum brasilense Sp6 known as root colonization bacteria, used as a positive control, randomly colonized the area of the rice root surface (rhizoplane), especially hairy root. By contrast, no bacterial cells of Escherichia coli BW25113 were detected (Fig. S5). Thus, we demonstrate, for the first time, that C. butyricum CC2 can colonize the rice root surface, which is an oxygen-enriched zone. To explore the effects of Clostridium species on plant physiology, we evaluated the ability of 18 Clostridium isolates to activate ISR in rice seedlings (Table S1). CC2, DG7, DG10, and DG12 were identified as ISR-positive strains, while IS21, IS13, CC3, and CJ17 were identified as ISR-negative strains. All the four ISR-positive strains significantly decreased the length of lesions caused by the rice bacterial blight pathogen, Xanthomonas oryzae pv oryzae (Xoo), by 52–72% compared with the control (Fig. 2a,b). This reduction in lesion length was similar to that caused by 0.05 mM benzothiadiazole treatment (positive control). Subsequently, under glasshouse conditions, lesion length was significantly reduced (41.1%) by CC2 treatment compared with the control (Figs 2c, S6a). Many ISR determinants produced by rhizobacteria have been reported previously include the cell membrane-localized exopolysaccharides and lipopolysaccharides as well as the secreted metabolites such as siderophores, salicylic acid, bacterial volatiles, and cyclic lipopeptides (Ryu et al., 2004; Nadarajah, 2016). Treatment with extracellular supernatant diluted 10-fold significantly decreased the lesion length by 85.3% compared with the control (Figs 2d, S6b). To identify specific ISR-related compounds in the supernatant of bacterial culture, we evaluated bacterial metabolites between ISR-positive and -negative strains (Fig. 2a) by liquid chromatography–mass spectrometry (LC–MS; Tyc et al., 2017). However, the LC–MS data showed no differences in metabolites between the two groups of strains (Fig. S6c). Previously, organic SCFAs and volatile compounds were identified as the major metabolites of Clostridium spp. (Vees et al., 2020). Therefore, we performed gas chromatography–mass spectrometry (GC–MS) analysis of the extracellular supernatant containing bacterial metabolites. Butyric acid was detected only in the supernatant of ISR-positive bacteria, C. butyricum CC2, C. guangxiense DG7, C. diolis DG10, and C. nigeriense DG12, but not in that of ISR-negative bacteria (Figs 2e, S6d). In addition, a strong correlation was detected between BA content and ISR capacity (P = 0.0357, R2 = 0.548; Fig. 2f). Next, we determined the minimum concentration of BA required for activating ISR. Application of 100 nM and 10 μM BA to rice root resulted in the greatest resistance to Xoo (Figs 2g, S7a). Notably, both 22:00 h and 1 mM BA showed similar biological activity, which was unusual. Further evaluation revealed no ISR at concentrations below 100 fM (Fig. S7b,c). These results indicate that 22:00 h BA is the minimum concentration required to elicit ISR. 100 nM and 10 μM BA were the most effective concentrations against Xoo (Fig. 2g). In addition, while 100 nM BA was undetectable due to the detection limit of GC–MS, it elicited ISR in rice (Figs S8, 2g). When we tested whether BA with volatile properties directly affects the growth of Xoo inoculated into leaves, we found that treatment with BA at concentrations ranging from 13:00 h to 1 mM did not inhibit the growth of Xoo (Fig. S9a). In 100 nM and 10 μM BA treatments, the expression of Pathogenesis-related 1b (PR1b) increased by 1.34- and 1.83-fold, respectively, at 12 h post-inoculation (hpi) compared with the control (Fig. 2h), indicating the activation of defense priming. Next, we asked whether strain CC2 could produce BA under in situ conditions (paddy soil). Unlike our expectation, the detectable amount of BA decreased with time, and the minimum amount was detected on day 7 (Fig. S9b). However, an additional analysis revealed that 100 nM BA could not be detected by GC–MS (Fig. S8). Our result suggests that BA-elicited ISR can occur even below the GC–MS detection limit when BA is produced by Clostridium in soil (Figs 2g, S8). Altogether, these results suggest that BA produced by C. butyricum strain CC2 is critical for triggering ISR. Because BA produced by Clostridium could not be detected in soil, we used an indirect approach to evaluate in situ BA biosynthesis in response to rice root exudates by examining the expression of bacterial BA biosynthesis-related genes, butyrate kinase (buk) and phosphotransbutyrase (ptb; Fig. 2i,j). BA is synthesized from glucose via the BUK pathway, in which PTB phosphorylates butyryl-CoA to form butyryl phosphate, which is then converted to butyrate by BUK, the final enzyme in this pathway. At 30 min after treatment with the root exudates of 7- and 14-d-old rice seedlings, the expression of buk increased by 1.4-and 1.53-fold, respectively (Fig. 2i), whereas that of ptb increased by 1.48- and 1.33-fold, respectively (Fig. 2j). Root exudates contain many organic substances including sugars, which are also essential for recruiting rhizobacteria (Bais et al., 2006). Therefore, these results suggest that CC2 can produce BA and trigger ISR by interacting with rice roots. Collectively, we demonstrate that Clostridium spp. (mostly obligate anaerobes) function as PGPR, and that Clostridium spp. produce BA. Additional interesting questions remain: how do Clostridium spp. interact with other anaerobic and aerobic bacteria in soil?; what is the direct effect of BA on rice soil microbiome?; and what other bacterial determinants, if any, activate plant immunity under anaerobic conditions?. Further studies are needed to investigate the effects of Clostridium spp. on upland crops such as wheat, pepper, and tomato. Given their critical advantage, such as ability to maintain stable spore formation under aerobic conditions, allowing their preparation before their application in fields, Clostridium spp. could have potential as a biofertilizer and bioprotective agent that only germinates under anaerobic conditions, such as the rice rhizosphere. The National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2021M3A9I5021439); Cooperative Research Program for Agriculture Science and Technology Development (Project no. PJ016990022023) of Rural Development Administration; Strategic Initiative for Microbiomes in Agriculture and Food, Ministry of Agriculture, Food and Rural Affairs, S. Korea (as part of the multi-ministerial Genome Technology to Business Translation Program 918017-4) and KRIBB Initiative Program, South Korea. None declared. CMR designed the study; S-HJ, MR, SL and J-SJ performed the experiments; S-HJ and J-SK analyzed the data; S-HJ and C-MR wrote the manuscript. The data that support the findings of this study are available from the corresponding author upon reasonable request. Fig. S1 Total principal coordinate analysis of rhizocompartments at five sites. Fig. S2 Clostridium spp. enriched in the rhizosphere of rice. Fig. S3 Aerobic bacteria enriched in the endosphere of rice. Fig. S4 Isolation of 18 Clostridium species from rice rhizocompartments. Fig. S5 Root colonization of Clostridium butyricum CC2. Fig. S6 Supernatant analysis of induced systemic resistance-positive and -negative strains by liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. Fig. S7 Butyric acid elicits induced systemic resistance against X. oryzae pv oryzae in rice. Fig. S8 Evaluation of detection limit of butyric acid using gas chromatography–mass spectrometry-headspace solid phase microextraction. Fig. S9 Direct and indirect effects of butyric acid on growth of Xoo. Notes S1 Details of the methods. Table S1 List of Clostridium species isolated from the different rhizocompartments of rice. Table S2 PCR primers used in this paper. Video S1 Colonization of Clostridium butyricum CC2 on the rice root surface. Please note: Wiley is not responsible for the content or functionality of any Supporting Information supplied by the authors. Any queries (other than missing material) should be directed to the New Phytologist Central Office. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Alterations in the intestinal microbial flora are known to cause various diseases, and many people routinely consume probiotics or prebiotics to balance intestinal microorganisms and the growth of beneficial bacteria. In this study, we selected a peptide from fish (tilapia) skin that induces significant changes in the intestinal microflora of mice and reduces the Firmicutes/Bacteroidetes ratio, which is linked to obesity. We attempted to verify the anti-obesity effect of selected fish collagen peptides in a high-fat-diet-based obese mouse model. As anticipated, the collagen peptide co-administered with a high-fat diet significantly inhibited the increase in the Firmicutes/Bacteroidetes ratio. It increased specific bacterial taxa, including Clostridium_sensu_stricto_1, Faecalibaculum, Bacteroides, and Streptococcus, known for their anti-obesity effects. Consequently, alterations in the gut microbiota resulted in the activation of metabolic pathways, such as polysaccharide degradation and essential amino acid synthesis, which are associated with obesity inhibition. In addition, collagen peptide also effectively reduced all obesity signs caused by a high-fat diet, such as abdominal fat accumulation, high blood glucose levels, and weight gain. Ingestion of collagen peptides derived from fish skin induced significant changes in the intestinal microflora and is a potential auxiliary therapeutic agent to suppress the onset of obesity.

First, we demonstrated that the presence of Enterococcus spp. is a driving force for insect metamorphosis. RNA sequencing and peptide production subsequently revealed that antimicrobial peptides targeted against microorganisms in the gut of Galleria mellonella (wax moth) did not kill Enterobacteria species, but did kill Enterococcus species, when the moth was at a certain stage of growth, and this promoted moth pupation.

BACKGROUND Although polymyxin has been used as a last-resort antibiotic against resistant bacteria, its use is restricted due to nephrotoxicity and neurotoxicity. While the present antibiotic resistance issue compels clinicians to reconsider polymyxin use in severe illness cases, polymyxin-resistant microorganisms exert an effect. OBJECTIVES To address the issue of antibiotic resistance, the cycle of developing new antibiotics to counteract emerging resistance must be discontinued. Here we tried to develop novel therapies that do not rely on direct antimicrobial activity and thus do not promote antibiotic resistance. METHODS By a high-throughout screening system based on bacterial respiration, chemical compounds accelerating the antimicrobial effects of polymyxin B were screened. In vitro and in vivo tests were performed to validate adjuvanticity. In addition, membrane depolarization and total transcriptome analysis were used to determine molecular mechanisms. RESULTS PA108, a newly discovered chemical compound, was used to eradicate polymyxin-resistant A. baumannii and three other species in the presence of polymyxin B at concentrations less than the MIC. Since this molecule lacks self-bactericidal action, we hypothesized that PA108 acts as an antibiotic adjuvant, enhancing the antimicrobial activity of polymyxin B against resistant bacteria. At working concentrations, no toxicity was observed in cell lines or mice, although co-treatment with PA108 and polymyxin B increased survival of infected mouse and decreased bacterial loads in organs. CONCLUSIONS Boosting antibiotic efficiency through the use of antibiotic adjuvants holds significant promise for tackling the rise in bacterial antibiotic resistance.

Since its initial report in Vietnam in early 2019, the African swine fever (ASF), a highly lethal and severe viral swine disease worldwide, continues to cause outbreaks in other Southeast Asian countries. This study analyzed and compared the genomic sequences of ASF viruses (ASFVs) during the first outbreak in Hung Yen (VN/HY/2019-ASFV1) and Quynh Phu provinces (VN/QP/2019-ASFV1) in Vietnam in 2019, and the subsequent outbreak in Hung Yen (VN/HY/2022-ASFV2) in 2022, to those of other ASFV strains. VN/HY/2019-ASFV1, VN/QP/2019-ASFV1, and VN/HY/2022-ASFV2 genomes were 189,113, 189,081, and 189,607 bp in length, encoding 196, 196, and 203 open reading frames (ORFs), respectively. VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1 shared a 99.91–99.99% average nucleotide identity with genotype II strains. Variations were identified in 28 ORFs in VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1 compared to 20 ASFV strains, and 16 ORFs in VN/HY/2022-ASFV2 compared to VN/HY/2019-ASFV1 and VN/QP/2019-ASFV1. Vietnamese ASFV genomes were classified as IGR II variants between the I73R and I329L genes, with two copy tandem repeats between the A179L and A137R genes. A phylogenetic analysis based on the whole genomes of 27 ASFV strains indicated that the Vietnamese ASFV strains are genetically related to Estonia 2014, ASFV-SY18, and Russia/Odintsovo_02/14. These results reveal the complete genome sequences of ASFV circulating during the first outbreak in 2019, providing important insights into understanding the evolution, transmission, and genetic variation of ASFV in Vietnam.

IntroductionGreen banana flour can be used as a prebiotic due to its ability to promote gut health and provide several health benefits. In this study, we investigated whether feeding mice green banana flour at different doses would alter intestinal microbiota composition.MethodsWe fed C57BL/6N mice either a Low-dose (500 mg/kg/day) or High-dose (2000 mg/kg/day) of green banana flour daily for 3 weeks, and fecal samples were collected on days 0, 14, and 21 for microbiota analysis.ResultsOur results showed that the composition of intestinal microbiota was significantly altered by day 21, regardless of the dose. Notably, the consumption of green banana flour increased the presence of beneficial bacteria, including Coriobacteriaceae_UCG-002, Turicibacter, Parasutterella, Gastranaerophilales_ge, and RF39_ge. These changes in the intestinal microorganisms were accompanied by increased biological processes such as amino acid biosynthesis and secondary metabolite biosynthesis. Conversely, the consumption of green banana flour resulted in a decrease in biological processes related to carbohydrate degradation, glycerol degradation, and similar functions.DiscussionThese results emphasize the potential of green banana flour as a prebiotic that can benefit the gut microbiome.

After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although the gut microbiome has been associated with cognitive function, it remains to be elucidated whether fecal microbiota transplantation can improve cognition in patients with cognitive decline. The study included 10 patients (age range, 63-90 years; female, 80%) with dementia and severe CDI who were receiving FMT. Also, 10 patients (age range, 62-91; female, 80%) with dementia and severe CDI who were not receiving FMT. They were evaluated using cognitive function tests (Mini-Mental State Examination [MMSE] and Clinical Dementia Rating scale Sum of Boxes [CDR-SB]) at 1 month before and after FMT or antibiotics treatment (control group). The patients' fecal samples were analyzed to compare the composition of their gut microbiota before and 3 weeks after FMT or antibiotics treatment. Ten patients receiving FMT showed significantly improvements in clinical symptoms and cognitive functions compared to control group. The MMSE and CDR-SB of FMT group were improved compare to antibiotics treatment (MMSE: 16.00, median, 13.00-18.00 [IQR] vs. 10.0, median, 9.8-15.3 [IQR]); CDR-SB: 5.50, median, 4.00-8.00 [IQR]) vs. 8.0, median, 7.9-12.5, [IQR]). FMT led to changes in the recipient's gut microbiota composition, with enrichment of Proteobacteria and Bacteroidetes. Alanine, aspartate, and glutamate metabolism pathways were also significantly different after FMT. This study revealed important interactions between the gut microbiome and cognitive function. Moreover, it suggested that FMT may effectively delay cognitive decline in patients with dementia.

RATIONALE Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established. PATIENT CONCERNS AND DIAGNOSIS We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection. INTERVENTIONS FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8weeks after FMT. OUTCOMES We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS. LESSONS Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.

Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life-threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O-GlcNAcylation, a type of post-translational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx-mediated increase in O-GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx-susceptible cells. The protective effect of O-GlcNAc inhibition for Stx-mediated pathogenic responses was also verified using three-dimensional (3D)-cultured spheroids or organoids mimicking the human kidney. Treatment with an O-GlcNAcylation inhibitor remarkably improved the major disease symptoms and survival rate for mice intraperitoneally injected with a lethal dose of Stx. In conclusion, this study elucidates O-GlcNAcylation-dependent pathogenic mechanisms of Stxs and demonstrates that inhibition of aberrant O-GlcNAcylation is a potential approach to treat Stx-mediated diseases.

After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although it is known that the gut microbiome is linked with cognitive function, whether FMT may lead to cognitive improvement in patients with neurodegenerative disorders remains to be elucidated. We present the case of a 90-year-old woman with Alzheimer's dementia and severe CDI who underwent FMT. Cognitive function testing (Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating assessment) was performed one month before FMT and one week and one month after FMT. We collected the patients' fecal samples before FMT and 3 weeks after FMT to compare the microbiota composition. The 16S rRNA gene amplicons were analyzed using the QIIME2 platform (version 2020.2) and the Phyloseq R package. The linear discriminant analysis effect size was performed to determine the taxonomic difference between pre- and post-FMT. Functional biomarker analysis using the Kruskal-Wallis H test was performed between the pre- and post-FMT. The cognitive function tests after FMT showed an improvement compared to the tests before the procedure. FMT changed the microbiota composition in recipient feces. We found that the genera were reported to be associated with cognitive function. In addition, short-chain fatty acids were found to be significantly different between before and after FMT. This finding suggests the presence of an association between the gut microbiome and cognitive function. Further, it emphasizes the need for clinical awareness regarding the effect of FMT on the brain-gut-microbiome axis and its potential as a therapy for patients with dementia.

In this study, a convenient high-performance portable sensor platform for simple, fast, and efficient detection of H1N1 virus is demonstrated using a graphene-based transistor type architecture. A uniform graphene layer was generated and patterned by conventional methods such as lithography and vapor deposition, subsequently, electrodes were introduced on the patterned graphene layer to obtain transistor type sensor geometry. Then, the graphene surface was functionalized with antibody for H1N1 virus detection and sensor performance test. The transition curve, linearity, and sensitivity (10 pfu/mL) of the sensor component were measured. In addition, the portable H1N1 diagnosis platform for simple, fast, and convenient virus detection was produced and demonstrated. Consequently, the sensor performance was maintained in the portable sensor platform compared with the graphene-based sensor component. This presented portable H1N1 diagnosis platform showed better performance than the lateral flow assay.