High-Precision Tailored Polymer Molecular Weights for Specific Photovoltaic Applications through Ultrasound-Induced Simultaneous Physical and Chemical Events.

It is highly challenging to reproducibly prepare semiconducting polymers with targeted molecular weight tailored for next-generation photovoltaic applications. Once such an easily accessible methodology is established, which can not only contribute to overcome the current limitation of the statistically determined nature of semiconducting polymers, but also facilitate rapid incorporation into the broad synthetic chemists' toolbox. Here, we describe a simple yet robust ultrasonication-assisted Stille polymerization for accessing semiconducting polymers with high-precision tailored molecular weights (from low to ultrahigh molecular weight ranges) while mitigating their interbatch variations. We propose that ultrasound-induced simultaneous physical and chemical events enable precise control of the semiconducting polymers' molecular weights with high reproducibility to satisfy all the optical/electrical and morphological demands of diverse types of high-performance semiconducting polymer-based devices; as demonstrated in in-depth experimental screenings in applications of both organic and perovskite photovoltaics. We believe that this methodology provides a fast development of new and existing semiconducting polymers with the highest-level performances possible on various photovoltaic devices.

Assessment of DNA extraction methods for human gut mycobiome analysis.

The gut mycobiome plays an important role in the health and disease of the human gut, but its exact function is still under investigation. While there is a wealth of information available on the bacterial community of the human gut microbiome, research on the fungal community is still relatively limited. In particular, technical methodologies for mycobiome analysis, especially the DNA extraction method for human faecal samples, varied in different studies. In the current study, two commercial kits commonly used in DNA extraction, the QIAamp® Fast DNA Stool Mini Kit and DNeasy PowerSoil Pro Kit, and one manual method, the International Human Microbiome Standards Protocol Q, were compared. Furthermore, the effectiveness of two different bead-beating machines, the Mini-Beadbeater-16 and FastPrep-24TM 5G, was compared in parallel. A mock fungal community with a known composition of fungal strains was also generated and included to compare different DNA extraction methods. Our results suggested that the method using the DNeasy PowerSoil Pro Kit and Mini-Beadbeater-16 provides the best results to extract DNA from human faecal samples. Based on our data, we propose a standard operating procedure for DNA extraction from human faecal samples for mycobiome analysis.

Highly Efficient Nitrogen-Fixing Microbial Hydrogel Device for Sustainable Solar Hydrogen Production.

Conversion of sunlight and organic carbon substrates to sustainable energy sources through microbial metabolism has great potential for the renewable energy industry. Despite recent progress in microbial photosynthesis, the development of microbial platforms that warrant efficient and scalable fuel production remains in its infancy. Efficient transfer and retrieval of gaseous reactants and products to and from microbes are particular hurdles. Here, inspired by water lily leaves floating on water, a microbial device designed to operate at the air-water interface and facilitate concomitant supply of gaseous reactants, smooth capture of gaseous products, and efficient sunlight delivery is presented. The floatable device carrying Rhodopseudomonas parapalustris, of which nitrogen fixation activity is first determined through this study, exhibits a hydrogen production rate of 104 mmol h-1  m-2 , which is 53 times higher than that of a conventional device placed at a depth of 2 cm in the medium. Furthermore, a scaled-up device with an area of 144 cm2 generates hydrogen at a high rate of 1.52 L h-1  m-2 . Efficient nitrogen fixation and hydrogen generation, low fabrication cost, and mechanical durability corroborate the potential of the floatable microbial device toward practical and sustainable solar energy conversion.

Environmental Adaptation of Psychrophilic Bacteria Subtercola spp. Isolated from Various Cryospheric Habitats.

Subtercola boreus K300T is a novel psychrophilic strain that was isolated from permanently cold groundwater in Finland and has also been found in several places in Antarctica including lake, soil, and rocks. We performed genomic and transcriptomic analyses of 5 strains from Antarctica and a type strain to understand their adaptation to different environments. Interestingly, the isolates from rocks showed a low growth rate and smaller genome size than strains from the other isolation sources (lake, soil, and groundwater). Based on these habitat-dependent characteristics, the strains could be classified into two ecotypes, which showed differences in energy production, signal transduction, and transcription in the clusters of orthologous groups of proteins (COGs) functional category. In addition, expression pattern changes revealed differences in metabolic processes, including uric acid metabolism, DNA repair, major facilitator superfamily (MFS) transporters, and xylose degradation, depending on the nutritional status of their habitats. These findings provide crucial insights into the environmental adaptation of bacteria, highlighting genetic diversity and regulatory mechanisms that enable them to thrive in the cryosphere.

Conformational Locking Control of 2D Outer Side Chains via Fluorine Atom Positioning for Improving the Thermal Stability of Organic Solar Cells.

Alongside high power conversion efficiencies (PCEs), device stability, especially thermal issues, is another key factor for the successful commercialization of nonfullerene acceptor (NFA)-based organic solar cells (OSCs). Considering the significant effects of the side-chain engineering of NFAs on molecular packing and/or locking strongly associated with the thermal stability of OSCs, herein, we present two new isomeric NFAs with 4-fluoro- and 2-fluoro-substituted hexylphenyl two-dimensional (2D) outer side chains (4FY and 2FY, respectively). In contrast with the 2FY having a horizontal stretching conformation, 4FY exhibits a diagonal stretching conformation of the 2D outer side chains and a higher dipole moment, resulting in a huge difference in their crystalline/aggregation characteristics, i.e., 4FY possesses a higher crystallinity with a denser molecular packing than the 2FY neat film, as evidenced by thermal and morphological characterizations. Encouragingly, relative to the one based on 2FY, the OSC based on 4FY delivers a PCE as high as 16.4%, together with excellent thermal stability (88.4% PCE retention under 85 °C for 360 h), which is attributed to a more optimal and robust blend morphology induced by its better compatibility into the used donor component and stronger crystallinity. This work demonstrates that in addition to the improved photovoltaic property, the appropriate F-positioning on the 2D outer side chains can play a key role in controlling their conformations, which can promote the increase of the thermal stability of OSCs.

Regulating the Sequence Structure of Conjugated Block Copolymers Enables Large-Area Single-Component Organic Solar Cells with High Efficiency and Stability.

Single-component organic solar cells (SCOSCs) based on conjugated block copolymers (CBCs) by covalently bonding a polymer donor and polymer acceptor become more and more appealing due to the formation of a favorable and stable morphology. Unfortunately, a deep understanding of the effect of the assembly behavior caused by the sequence structure of CBCs on the device performance is still missing. Herein, from the aspect of manipulating the sequence length and distribution regularity of CBCs, we synthesized a series of new CBCs, namely D18(20)-b-PYIT, D18(40)-b-PYIT and D18(60)-b-PYIT by two-pot polymerization, and D18(40)-b-PYIT(r) by traditional one-pot method. It is observed that precise manipulation of sequence length and distribution regularity of the polymer blocks fine-tunes the self-assembly of the CBCs, optimizes film morphology, improves optoelectronic properties, and reduces energy loss, leading to simultaneously improved efficiency and stability. Among these CBCs, the D18(40)-b-PYIT-based device achieves a high efficiency of 13.4 % with enhanced stability, which is an outstanding performance among SCOSCs. Importantly, the regular sequence distribution and suitable sequence length of the CBCs enable a facile film-forming process of the printed device. For the first time, the blade-coated large-area rigid/flexible SCOSCs are fabricated, delivering an impressive efficiency of 11.62 %/10.73 %, much higher than their corresponding binary devices.

Regulation of acetate tolerance by small ORF-encoded polypeptides modulating efflux pump specificity in Methylomonas sp. DH-1.

BACKGROUND: Methanotrophs have emerged as promising hosts for the biological conversion of methane into value-added chemicals, including various organic acids. Understanding the mechanisms of acid tolerance is essential for improving organic acid production. WatR, a LysR-type transcriptional regulator, was initially identified as involved in lactate tolerance in a methanotrophic bacterium Methylomonas sp. DH-1. In this study, we investigated the role of WatR as a regulator of cellular defense against weak organic acids and identified novel target genes of WatR. RESULTS: By conducting an investigation into the genome-wide binding targets of WatR and its role in transcriptional regulation, we identified genes encoding an RND-type efflux pump (WatABO pump) and previously unannotated small open reading frames (smORFs), watS1 to watS5, as WatR target genes activated in response to acetate. The watS1 to watS5 genes encode polypeptides of approximately 50 amino acids, and WatS1 to WatS4 are highly homologous with one predicted transmembrane domain. Deletion of the WatABO pump genes resulted in decreased tolerance against formate, acetate, lactate, and propionate, suggesting its role as an efflux pump for a wide range of weak organic acids. WatR repressed the basal expression of watS genes but activated watS and WatABO pump genes in response to acetate stress. Overexpression of watS1 increased tolerance to acetate but not to other acids, only in the presence of the WatABO pump. Therefore, WatS1 may increase WatABO pump specificity toward acetate, switching the general weak acid efflux pump to an acetate-specific efflux pump for efficient cellular defense against acetate stress. CONCLUSIONS: Our study has elucidated the role of WatR as a key transcription factor in the cellular defense against weak organic acids, particularly acetate, in Methylomonas sp. DH-1. We identified the genes encoding WatABO efflux pump and small polypeptides (WatS1 to WatS5), as the target genes regulated by WatR for this specific function. These findings offer valuable insights into the mechanisms underlying weak acid tolerance in methanotrophic bacteria, thereby contributing to the development of bioprocesses aimed at converting methane into value-added chemicals.

Naphthalene diimide-based random terpolymers with axisymmetric and asymmetric electron acceptors for controllable morphology and enhanced fill factors in all-polymer solar cells.

All-polymer solar cells (all-PSCs), based on p-type polymer donors and n-type acceptors as the active layer, offer exceptional promise because of excellent thermal stability, superior film formation, and good mechanical stress as a unique bulk heterojunction (BHJ) solar cell combination. Therefore, tuning the molecular composition between polymers is crucial for optimizing power conversion efficiency (PCE) in these all-PSC systems. In this study, we synthesized a series of naphthalene diimide (NDI)-based random terpolymers P(NDI-BDD10), P(NDI-TPD10), P(NDI-TT10), and P(NDI-2FQ10) with axisymmetric (BDD, TPD) and asymmetric (TT, 2FQ) electron acceptors. Compared with the blend morphology of PBDB-T:N2200, their diverse effects due to the addition of trace amounts of axisymmetric and asymmetric components were comprehensively investigated using physical and surface analyses and structural simulations. Consequently, most of our polymer acceptors demonstrated improved fill factors (FFs) in the optimal morphology. P(NDI-BDD10)-based devices achieved the highest PCE of 6.80% and FF of 69.1%, while the architecturally most asymmetric P(NDI-TT10)-based devices reached the lowest PCE of 4.52% despite an enhanced FF of 65.4%. As a result, the appropriate molecular arrangement is crucial for obtaining the desired morphology and improved PCE. Our findings give novel molecular design insight into the distinctions between axisymmetric and asymmetric electron acceptors and seem significant for achieving improved morphological features and efficiency.

Anthradithiophene (ADT)-Based Polymerized Non-Fullerene Acceptors for All-Polymer Solar Cells.

Realizing efficient all-polymer solar cell (APSC) acceptors typically involves increased building block synthetic complexity, hence potentially unscalable syntheses and/or prohibitive costs. Here we report the synthesis, characterization, and implementation in APSCs of three new polymer acceptors P1-P3 using a scalable donor fragment, bis(2-octyldodecyl)anthra[1,2-b : 5,6-b']dithiophene-4,10-dicarboxylate (ADT) co-polymerized with the high-efficiency acceptor units, NDI, Y6, and IDIC. All three copolymers have comparable photophysics to known polymers; however, APSCs fabricated by blending P1, P2 and P3 with donor polymers PM5 and PM6 exhibit modest power conversion efficiencies (PCEs), with the champion P2-based APSC achieving PCE=5.64 %. Detailed morphological and microstructural analysis by AFM and GIWAXS reveal a non-optimal APSC active layer morphology, which suppresses charge transport. Despite the modest efficiencies, these APSCs demonstrate the feasibility of using ADT as a scalable and inexpensive electron rich/donor building block for APSCs.

Dithieno[3,2-f:2',3'-h]quinoxaline-Based Photovoltaic-Thermoelectric Dual-Functional Energy-Harvesting Wide-Bandgap Polymer and its Backbone Isomer.

Both organic solar cells (OSCs) and organic thermoelectrics (OTEs) are promising energy-harvesting technologies for future renewable and sustainable energy sources. Among various material systems, organic conjugated polymers are an emerging material class for the active layers of both OSCs and OTEs. However, organic conjugated polymers showing both OSC and OTE properties are rarely reported because of the different requirements toward the OSCs and OTEs. In this study, the first simultaneous investigation of the OSC and OTE properties of a wide-bandgap polymer PBQx-TF and its backbone isomer iso-PBQx-TF are reported. All wide-bandgap polymers form face-on orientations in a thin-film state, but PBQx-TF has more of a crystalline character than iso-PBQx-TF, originating from the backbone isomeric structures of α,α '/ß,ß '-connection between two thiophene rings. Additionally, iso-PBQx-TF shows inactive OSC and poor OTE properties, probably because of the absorption mismatch and unfavorable molecular orientations. At the same time, PBQx-TF exhibits both decent OSC and OTE performances, indicating that it satisfies the requirements for both OSCs and OTEs. This study presents the OSC and OTE dual-functional energy-harvesting wide-bandgap polymer and the future research directions for hybrid energy-harvesting materials.

Protective role of colitis in inflammatory arthritis via propionate-producing Bacteroides in the gut.

Objectives: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events. Methods: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis. Results: Contrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, Bacteroides vulgatus and its higher taxonomic ranks were enriched in the DSS-treated mice. B. vulgatus, B. caccae, and B. thetaiotaomicron exerted anti-arthritic effects. Propionate production deficiency further prevented the protective effect of B. thetaiotaomicron on arthritis. Conclusions: We suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producing Bacteroides species examined in this study may be a potential candidate for developing effective treatments for inflammatory arthritis.

Transcriptional Interplay between Malassezia restricta and Staphylococcus Species Co-Existing in the Skin Environment.

Malassezia and Staphylococcus are the most dominant genera in human skin microbiome. To explore the inter-kingdom interactions between the two genera, we examined the transcriptional changes in Malassezia and Staphylococcus species induced upon co-culturing. RNA-seq analyses revealed that genes encoding ribosomal proteins were upregulated, while those encoding aspartyl proteases were downregulated in M. restricta after co-culturing with Staphylococcus species. We identified MRET_3770 as a major secretory aspartyl protease coding gene in M. restricta through pepstatin-A affinity chromatography followed by mass spectrometry and found that the expression of MRET_3770 was significantly repressed upon co-culturing with Staphylococcus species or by incubation in media with reduced pH. Moreover, biofilm formation by Staphylococcus aureus was inhibited in the spent medium of M. restricta, suggesting that biomolecules secreted by M. restricta such as secretory aspartyl proteases may degrade the biofilm structure. We also examined the transcriptional changes in S. aureus co-cultured with M. restricta and found co-cultured S. aureus showed increased expression of genes encoding ribosomal proteins and downregulation of those involved in riboflavin metabolism. These transcriptome data of co-cultured fungal and bacterial species demonstrate a dynamic interplay between the two co-existing genera.

Large Transconductance of Electrochemical Transistors Based on Fluorinated Donor-Acceptor Conjugated Polymers.

Organic electrochemical transistors (OECTs) have enormous potential for use in biosignal amplifiers, analyte sensors, and neuromorphic electronics owing to their exceptionally large transconductance. However, it is challenging to simultaneously achieve high charge carrier mobility and volumetric capacitance, the two most important figures of merit in OECTs. Herein, a method of achieving high-performance OECT with donor-acceptor conjugated copolymers by introducing fluorine units is proposed. A series of cyclopentadithiophene-benzothiadiazole (CDT-BT) copolymers for use in high-performance OECTs with enhanced charge carrier mobility (from 0.65 to 1.73 cm2·V-1·s-1) and extended volumetric capacitance (from 44.8 to 57.6 F·cm-3) by fluorine substitution is achieved. The increase in the volumetric capacitance of the fluorinated polymers is attributed to either an increase in the volume at which ions can enter the film or a decrease in the effective distance between the ions and polymer backbones. The fluorine substitution increases the backbone planarity of the CDT-BT copolymers, enabling more efficient charge carrier transport. The fluorination strategy of this work suggests the more versatile use of conjugated polymers for high-performance OECTs.

Revealing the Enhanced Thermoelectric Properties of Controllably Doped Donor-Acceptor Copolymer: The Impact of Regioregularity.

Albeit considerable attention to the fast-developing organic thermoelectric (OTE) materials due to their flexibility and non-toxic features, it is still challenging to design an OTE polymer with superior thermoelectric properties. In this work, two "isomorphic" donor-acceptor (D-A) conjugated polymers are studied as the semiconductor in OTE devices, revealing for the first time the internal mechanism of regioregularity on thermoelectric performances in D-A type polymers. A higher molecular structure regularity can lead to higher crystalline order and mobility, higher doping efficiency, order of energy state, and thermoelectric (TE) performance. As a result, the regioregular P2F exhibits a maximum power factor (PF) of up to 113.27 µW m-1  K-2 , more than three times that of the regiorandom PRF (35.35 µW m-1  K-2 ). However, the regular backbone also implies lower miscibility with a dopant, negatively affecting TE performance. Therefore, the trade-off between doping efficiency and miscibility plays a vital role in OTE materials, and this work sheds light on the molecular design strategy of OTE polymers with state-of-the-art performances.

Mycobacterium potentiates protection from colorectal cancer by gut microbial alterations.

Not only are many Mycobacteria pathogens, but they can act as strong non-specific immunopotentiators, generating beneficial effects on the pathogenesis of some diseases. However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat-killed Mycobacterial tuberculosis and live Mycobacterium bovis (Bacillus Calmette-Guérin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the Reg3 family genes. Furthermore, interleukin-22 production by T helper cells contributed to the anti-inflammatory activity of Mycobacteria. Our results revealed a novel role of Mycobacteria involving gut microbial alterations in dampening inflammation-associated CRC and an immunological mechanism underlying the interaction between microbes and host immunity.

A mannose-sensing AraC-type transcriptional activator regulates cell-cell aggregation of Vibrio cholerae.

In addition to catalyzing coupled transport and phosphorylation of carbohydrates, the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulates various physiological processes in most bacteria. Therefore, the transcription of genes encoding the PTS is precisely regulated by transcriptional regulators depending on substrate availability. As the distribution of the mannose-specific PTS (PTSMan) is limited to animal-associated bacteria, it has been suggested to play an important role in host-bacteria interactions. In Vibrio cholerae, mannose is known to inhibit biofilm formation. During host infection, the transcription level of the V. cholerae gene encoding the putative PTSMan (hereafter referred to as manP) significantly increases, and mutations in this gene increase host survival rate. Herein, we show that an AraC-type transcriptional regulator (hereafter referred to as ManR) acts as a transcriptional activator of the mannose operon and is responsible for V. cholerae growth and biofilm inhibition on a mannose or fructose-supplemented medium. ManR activates mannose operon transcription by facilitating RNA polymerase binding to the promoter in response to mannose 6-phosphate and, to a lesser extent, to fructose 1-phosphate. When manP or manR is impaired, the mannose-induced inhibition of biofilm formation was reversed and intestinal colonization was significantly reduced in a Drosophila melanogaster infection model. Our results show that ManR recognizes mannose and fructose in the environment and facilitates V. cholerae survival in the host.

γ-Ester-Functionalized 1,1-Dicyanomethylene-3-indanone End-Capped Nonfullerene Acceptors for High-Performance, Annealing-Free Organic Solar Cells.

Modifying the end-capping groups in nonfullerene acceptors (NFAs) is an effective strategy for modulating their properties and that of the entire NFAs. This study reports the synthesis of a novel γ-ester-functionalized IC end-capping group (IC-γe) and its incorporation into the benzothiadiazole-fused central core, yielding isomer-free IC-γe end-capped NFAs, such as Y-IC-γe, Y-FIC-γe, and Y-ClIC-γe. The resultant NFAs exhibited similar absorption profiles but upshifted the lowest unoccupied molecular orbital energy level compared with those of the ester-free analogues, such as Y6 and Y7. Without thermal annealing, an excellent power conversion efficiency (PCE) of 16.4% is realized in the annealing-free OSC based on Y-FIC-γe with the PM6 donor polymer, which outperforms the OSCs based on Y-IC-γe and Y-ClIC-γe. In addition, the OSCs based on asymmetric Y-FIC-γe and Y-ClIC-γe have higher thermal stability with more than 83% PCE retention at an elevated temperature after 456 h than the symmetric Y-IC-γe case. In this study, we not only establish the structure-property relationship regarding the ester functionality and symmetricity tuning on the NFAs but also diagnose the reasons for the best-performing Y-FIC-γe-based OSCs, providing useful information for a novel high-performing NFA design strategy.

Genome of Malassezia arunalokei and Its Distribution on Facial Skin.

Malassezia is a fungal genus found on the skin of humans and warm-blooded animals, with 18 species reported to date. In this study, we sequenced and annotated the genome of Malassezia arunalokei, which is the most recently identified Malassezia species, and compared it with Malassezia restricta, the predominant isolate from human skin. Additionally, we reanalyzed previously reported mycobiome data sets with a species-level resolution to investigate M. arunalokei distribution within the mycobiota of human facial skin. We discovered that the M. arunalokei genome is 7.24 Mbp in size and encodes 4,117 protein-coding genes, all of which were clustered with M. restricta. We also found that the average nucleotide identity value of the M. arunalokei genome was 93.5, compared with the genomes of three M. restricta strains, including M. restricta KCTC 27527. Our findings demonstrate that they indeed belong to different species and that M. arunalokei may have experienced specific gene loss events during speciation. Furthermore, our study showed that M. arunalokei was diverged from M. restricta approximately 7.1 million years ago and indicated that M. arunalokei is the most recently diverged species in the Malassezia lineage to date. Finally, our analysis of the facial mycobiome of previously recruited cohorts revealed that M. arunalokei abundance is not associated with seborrheic dermatitis/dandruff or acne, but was revealed to be more abundant on the forehead and cheek than on the scalp. IMPORTANCEMalassezia is the fungus predominantly residing on the human skin and causes various skin diseases, including seborrheic dermatitis and dandruff. To date, 18 species have been reported, and among them, M. restricta is the most predominant on human skin, especially on the scalp. In this study, we sequenced and analyzed the genome of M. arunalokei, which is the most recently identified Malassezia species, and compared it with M. restricta. Moreover, we analyzed the fungal microbiome to investigate the M. arunalokei distribution on human facial skin. We found that M. arunalokei may have experienced specific gene loss events during speciation. Our study also showed that M. arunalokei was diverged from M. restricta approximately 7.1 million years ago and indicated that M. arunalokei is the most recently diverged species in the Malassezia lineage. Finally, our analysis of the facial mycobiome revealed that M. arunalokei has higher relative abundance on the forehead and cheek than the scalp.

A mucin-responsive hybrid two-component system controls Bacteroides thetaiotaomicron colonization and gut homeostasis.

The mammalian intestinal tract contains trillions of bacteria. However, the genetic factors that allow gut symbiotic bacteria to occupy intestinal niches remain poorly understood. Here, we identified genetic determinants required for Bacteroides thetaiotaomicron colonization in the gut using transposon sequencing analysis. Transposon insertion in BT2391, which encodes a hybrid two-component system, increased the competitive fitness of B. thetaiotaomicron. The BT2391 mutant showed a growth advantage in a mucin-dependent manner and had an increased ability to adhere to mucus-producing cell lines. The increased competitive advantage of the BT2391 mutant was dependent on the BT2392-2395 locus containing susCD homologs. Deletion of BT2391 led to changes in the expression levels of B. thetaiotaomicron genes during gut colonization. However, colonization of the BT2391 mutant promoted DSS colitis in low-fiber diet-fed mice. These results indicate that BT2391 contributes to a sustainable symbiotic relationship by maintaining a balance between mucosal colonization and gut homeostasis.

The human symbiont Bacteroides thetaiotaomicron promotes diet-induced obesity by regulating host lipid metabolism.

The gut microbiome plays an important role in lipid metabolism. Consumption of a high-fat diet (HFD) alters the bacterial communities in the gut, leading to metabolic disorders. Several bacterial species have been associated with diet-induced obesity, nonalcoholic fatty liver disease, and metabolic syndrome. However, the mechanisms underlying the control of lipid metabolism by symbiotic bacteria remain elusive. Here, we show that the human symbiont Bacteroides thetaiotaomicron aggravates metabolic disorders by promoting lipid digestion and absorption. Administration of B. thetaiotaomicron to HFD-fed mice promoted weight gain, elevated fasting glucose levels, and impaired glucose tolerance. Furthermore, B. thetaiotaomicron treatment upregulated the gene expression of the fatty acid transporter and increased fatty acid accumulation in the liver. B. thetaiotaomicron inhibits expression of the gene encoding a lipoprotein lipase inhibitor, angiopoietin-like protein 4 (ANGPTL4), thereby increasing lipase activity in the small intestine. In particular, we found that B. thetaiotaomicron induced the expression of hepcidin, the master regulator of iron metabolism and an antimicrobial peptide, in the liver. Hepcidin treatment resulted in a decrease in ANGPTL4 expression in Caco-2 cells, whereas treatment with an iron chelator restored ANGPTL4 expression in hepcidin-treated cells. These results indicate that B. thetaiotaomicron-mediated regulation of iron storage in intestinal epithelial cells may contribute to increased fat deposition and impaired glucose tolerance in HFD-fed mice.