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The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Fusobacterium vincentii usually inhabits the oral cavity and plays an important role in periodontal diseases. Here, we report the draft genome sequence of F. vincentii strain CNGBCC1850030, isolated from healthy human feces.

Bacteriophages and bacteria are engaged in a constant arms race, continually evolving new molecular tools to survive one another. To protect their genomic DNA from restriction enzymes, the most common bacterial defence systems, double-stranded DNA phages have evolved complex modifications that affect all four bases. This study focuses on modifications at position 7 of guanines. Eight derivatives of 7-deazaguanines were identified, including four previously unknown ones: 2’-deoxy-7-(methylamino)methyl-7-deazaguanine (mdPreQ1), 2’-deoxy-7-(formylamino)methyl-7-deazaguanine (fdPreQ1), 2’-deoxy-7-deazaguanine (dDG), and 2’-deoxy-7-carboxy-7-deazaguanine (dCDG). These modifications are inserted in DNA by a guanine transglycosylase named DpdA. Three subfamilies of DpdA had been previously characterized: bDpdA, DpdA1, and DpdA2. Two additional subfamilies were identified in this work: DpdA3, which allows for complete replacement of the guanines, and DpdA4, which is specific to archaeal viruses. Transglycosylases have now been identified in all phages and viruses carrying 7-deazaguanine modifications, indicating that the insertion of these modifications is a post-replication event. Three enzymes were predicted to be involved in the biosynthesis of these newly identified DNA modifications: 7-carboxy-7-deazaguanine decarboxylase (DpdL), dPreQ1formyltransferase (DpdN), and dPreQ1methyltransferase (DpdM), which was experimentally validated and harbors a unique fold not previously observed for nucleic acid methylases.

Abstract Plants produce various plant secondary compounds (PSCs) to deter the foraging of herbivorous mammals. However, little is known about whether PSCs can reshape gut microbiota and promote gut homeostasis of hosts. Using 16S rDNA sequencing to investigate the effects of PSCs on the gut microbiota of small herbivorous mammals, we studied plateau pikas (Ochotona curzoniae) fed diets containing swainsonine (SW) extracted from Oxytropis ochrocephala. Our results showed that both long- and short-term treatment of a single artificial diet in the laboratory significantly reduced alpha diversity and significantly affected beta diversity, core bacteria abundance, and bacterial functions in pikas. After SW was added to the artificial diet, the alpha diversity significantly increased in the long-term treatment, and core bacteria (e.g., Akkermansiaceae) with altered relative abundances in the two treatments showed no significant difference compared with pikas in the wild. The complexity of the co-occurrence network structure was reduced in the artificial diet, but it increased after SW was added in both treatments. Further, the abundances of bacteria related to altered alanine, aspartate, and glutamate metabolism in the artificial diet were restored in response to SW. SW further decreased the concentration of short-chain fatty acids (SCFAs) in both treatments. Our results suggest that PSCs play a key role in regulating gut microbiota community and intestinal homeostasis, thereby maintaining host health. Key points • Swainsonine improves the intestinal bacterial diversity of plateau pikas. • Swainsonine promotes the recovery of core bacterial abundances in the gut of plateau pikas. • Swainsonine promotes the restoration of intestinal bacterial functions of plateau pikas.

New Sn-Ti microspheres were first successfully synthesized by a PVP-assisted sol-gel method in this paper, and their performance in the B–V oxidation of cyclohexanone was investigated. The XRD, N2 sorption, SEM, Py-IR, UV–Vis, XPS, EDX, Elemental mapping and TEM characterization techniques were utilized to investigate their physical and chemical properties. Based on the proposal possible formation mechanism, in the MTS-x sample synthesis procedure, the introduction of PVP as a stabilizer and dispersant can coordinate the hydrolysis rate of two different precursors resulting in the hindrance of their agglomerations. And the HDA as a precipitation accelerator and morphology control agent can be beneficial to the formation of spheres by increasing the hydrogen-bonding interactions. The MTS-12 as well as the weight percent of tin to titanium species of 12 with specific regular microspheres has the highest cyclohexanone conversion of 97.8% and the highest e-caprolactone selectivity of 98.2%, which is better than the bulk Sn-TiO2 catalyst even though that the weight percent of tin to titanium species was 18. The catalysts with higher accessible active sites and shorter diffusion channels would provide a valuable theoretic reference for the industrial process of the B–V oxidation of cyclohexanone for the preparation of caprolactone.

Our study demonstrated that both host species identity and environments combine to shape the composition and function of gut microbiota in the herbivorous mammals. These findings imply that the sympatric herbivorous mammals may relax the interspecific relationship by reshaping the gut microbiota when the food is abundant in summer, and compete for limited food resources by advancing the capacity of gut microbiota in winter., Summary The previous studies have reported that the mammalian gut microbiota is a physiological consequence; nonetheless, the factors influencing its composition and function remain unclear. In this study, to evaluate the contributions of the host and environment to the gut microbiota, we conducted a sequencing analysis of 16S rDNA and shotgun metagenomic DNA from plateau pikas and yaks, two sympatric herbivorous mammals, and further compared the sequences in summer and winter. The results revealed that both pikas and yaks harboured considerably more distinct communities between summer and winter. We detected the over‐representation of Verrucomicrobia and Proteobacteria in pikas, and Archaea and Bacteroidetes in yaks. Firmicutes and Actinobacteria, associated with energy‐efficient acquisition, significantly enriched in winter. The diversity of the microbial community was determined by the interactive effects between the host and season. Metagenomic analysis revealed that methane‐metabolism‐related pathway of yaks was significantly enriched in summer, while some pathogenic pathways were more abundant in pikas. Both pikas and yaks had a higher capacity for lipid degradation in winter. Pika and yak shared more OTUs when food shortage occurred in winter, and this caused a convergence in gut microbial composition and function. From winter to summer, the network module number increased from one to five in pikas, which was different in yaks. Our study demonstrates that the host is a dominant factor in shaping the microbial communities and that seasonality promotes divergence or convergence based on dietary quality across host species identity.

A series of Sn–Ti(n)–DETA catalysts were prepared by a simple EISA method assisted by post-treatment of diethylenetriamine (DETA) solution, and several characterization techniques, including XRD, N2 sorption, Raman, ICP, UV–Vis DRS, pyridine-adsorbed IR, SEM, and TEM, were adopted to investigate their physical and chemical properties. The influence of DETA on the tin incorporation promotion of mesoporous Sn–Ti catalysts and their catalytic performance in the B–V oxidation of cyclohexanone by molecular oxygen were also studied. The mesopores with higher surface area and larger pore volume can be kept well when the weight percent of tetrahedrally incorporated tin species would be promoted up to 21% owing to the stronger alkalinity and more primary amine of the DETA molecule resulting in higher Lewis acidity. The cyclohexanone conversion of 95.5% and caprolactone selectivity of 96.8%, respectively, over Sn–Ti(21)–DETA catalyst were obtained, and it shows good catalytic stability even after reused for 5 times.

STT3 is a catalytic subunit of hetero‐oligomeric oligosaccharyltransferase (OST), which is important for asparagine‐linked glycosylation. In mammals and plants, OSTs with different STT3 isoforms exhibit distinct levels of enzymatic efficiency or different responses to stressors. Although two different STT3 isoforms have been identified in both plants and animals, it remains unclear whether these isoforms result from gene duplication in an ancestral eukaryote. Furthermore, the molecular mechanisms underlying the functional divergences between the two STT3 isoforms in plant have not been well elucidated. Here, we conducted phylogenetic analysis of the major evolutionary node species and suggested that gene duplications of STT3 may have occurred independently in animals and plants. Across land plants, the exon–intron structure differed between the two STT3 isoforms, but was highly conserved for each isoform. Most angiosperm STT3a genes had 23 exons with intron phase 0, while STT3b genes had 6 exons with intron phase 2. Characteristic motifs (motif 18 and 19) of STT3s were mapped to different structure domains in the plant STT3 proteins. These two motifs overlap with regions of high nonsynonymous‐to‐synonymous substitution rates, suggesting the regions may be related to functional difference between STT3a and STT3b. In addition, promoter elements and gene expression profiles were different between the two isoforms, indicating expression pattern divergence of the two genes. Collectively, the identified differences may result in the functional divergence of plant STT3s., STT3 is a catalytic subunit of oligosaccharyltransferase (OST) which is important for N‐glycosylation. Two subtypes of STT3 exist in animal and plant through independent duplications. An ancient separation of STT3 in the common ancestor of plants was discovered. Different elements in the promoters, distinct motifs, and auxiliary subunits may confer divergent catalytic ability on OST containing STT3a or STT3b.

Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood. We sampled 162 wild plateau pikas (Ochotona curzoniae) in 4 seasons over 2 and a half years and recorded the air temperature, precipitation, and nutrient content in edible vegetation at the sampling site. After conducting 16S rRNA and shotgun metagenomic sequencing, we found that the highest alpha diversity, the relative abundance of Firmicutes, and the simplest co-occurrence network occurred in winter, whereas the highest relative abundance of Proteobacteria and the most complex network structure were observed in spring. The highest relative abundance of Verrucomicrobiota and Spirochaetota was seen in summer and autumn, respectively. Air temperature, precipitation, and the contents of crude protein, crude fiber, and polysaccharide in vegetation had significant effects on the seasonal changes in gut microbiota. Diet contributed more to microbial variation than climatic factors. Metagenomic analysis revealed that the amino acid metabolism pathway and axillary activity enzymes were most abundant in summer, while abundance of carbohydrate-binding modules and carbohydrate esterases was highest in spring. These microbial variations were related to the changes in dietary nutrition, indicating that gut microbiota of plateau pika contribute to the efficient use of food resources. This study provides new evidence of how external environmental factors affect the intestinal environment of small mammals.

Many pieces of evidence show that the adaptive response of plants to salt stress requires the maturation of N-glycan on associated proteins. However, it is still little known about the salt-responsive glycoproteins that function in this process. In the present study, we identified salt-responsive glycoproteins in wild-type (WT) Arabidopsis and two mutants defective in N-glycan maturation, mns1 mns2 and cgl1. A total of 97 proteins with abundance changes of >1.5‐ or mns1 mns2 hardly form functional regulatory networks in STRING analysis. Comparably, the regulatory network in cgl1 was visible and shared overlapping with that in WT. Such difference may supply the evidence to partially explain the lower salt sensitivity of mutant cgl1 than mns1 mns2. We further confirmed that two N-glycosylation clients, peroxidases PRX32 and PRX34, were involved in the salt stress response since the double mutants showed enhanced salt sensitivity. Together, our study provided proteomic evidence that N-glycans are crucial for modulating stress-responsive protein levels, and several novel glycoproteins responsible for salt stress tolerance in Arabidopsis were listed. Data are available via ProteomeXchange with identifier PXD006893.

Background Aging is closely associated with the occurrence and development of many complex diseases such as cardiovascular conditions, type 2 diabetes, gastrointestinal (GI) and renal diseases. Detecting changes as early as possible in the human body due to aging is thus crucial significant to potentially mitigate its impacts on physical health. Methods Here, we present a comprehensive metagenome association study and serum metabolomics profiling in a registry Guangxi-Longevity cohort aged from 20–111 years (n=151) and Kunming cohort ages ranging from 20–80 years (n=80). Results We identified uremic toxins as key factors in serum metabolomics highly associated with aging, and this finding has been validated in an independent Kunming-Aging cohort aged from 20–80 years (n=80). We also observed that aging-associated systemic inflammation levels were positively associated with uremic toxins. Moreover, the increased Escherichia coli, Odoribacter splanchnicus, Bilophila wadsworthia and Parabacteroides spp. abundances were related to serum levels of uremic toxins, and the accumulating rate of uremic toxins and specific microbial species was robustly much slower in centenarians than in nonagenarians. We further investigated the frailty and health status in long-living individuals aged above 90 years, and found that the frailty status might be a putative extreme aging phenomenon characterized by novel uremic toxin accumulation patterns. Conclusions Our findings reveal novel potential links between gut microbiota alterations, uremic toxins and aging, and highlight the preponderance of gut microbiota and serum metabolism in aging.

Animal gut microbiomes can be clustered into &ldquo, enterotypes&rdquo, characterized by an abundance of signature genera. The characteristic determinants, stability, and resilience of these community clusters remain poorly understood. We used plateau pika (Ochotona curzoniae) as a model and identified three enterotypes by 16S rDNA sequencing. Among the top 15 genera, 13 showed significantly different levels of abundance between the enterotypes combined with different microbial functions and distinct fecal short-chain fatty acids. We monitored changes in the microbial community associated with the transfer of plateau pikas from field to laboratory and observed that feeding them a single diet reduced microbial diversity, resulting in a single enterotype with an altered composition of the dominant bacteria. However, microbial diversity, an abundance of some changed dominant genera, and enterotypes were partially restored after adding swainsonine (a plant secondary compound found in the natural diet of plateau pikas) to the feed. These results provide strong evidence that gut microbial diversity and enterotypes are directly related to specific diet, thereby indicating that the formation of different enterotypes can help animals adapt to complex food conditions. Additionally, natural plant secondary compounds can maintain dominant bacteria and inter-individual differences of gut microbiota and promote the resilience of enterotypes in small herbivorous mammals.

Neonatal cholestasis disease (NCD) is a complex and easily mis-diagnosed condition. We analyzed microbiota community structure in feces and measured short-chain fatty acids, bile acids (BAs) and liver function of 12 healthy, 13 NCD, and 13 treated infants after diagnosis. Based on 16S rRNA gene amplicon sequencing and gas-chromatographic-mass-spectrometric analysis of secondary BAs, we identified microbial genera and metabolites that associate with abnormal bile secretion. Streptococcus gallolyticus and Parabacteroides distasonis, and Lactobacillus gasseri had higher relative abundance in healthy and NCD infants respectively. Compared to NCD patients, healthy infants had higher LCA, CDCA and GCDCA fecal concentrations. The three microbial species and three secondary bile acids were selected as potential non-invasive combined biomarkers to diagnose NCD. We propose that microbiota-metabolite combined biomarkers could be used for diagnosis of NCD, and this may contribute to improved early clinical diagnosis of NCD in the future.

Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes. The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi. However, the biological importance of Golgi-mediated mannose trimming is not fully understood. Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis. In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming. However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant. Interestingly, we observed that cellulose biosynthesis was compromised in mns1 mns2 roots under high salinity. Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress. Overexpression of RSW2 could partially rescue the salt-sensitive phenotype of mns1 mns2. Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.