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Background Previous studies have identified a large number of distinct microbial taxa that are different between patients with multiple sclerosis (MS) and controls. However, interpretating findings on MS-associated microbiome is challenging as results do not completely concur and studies have included relatively few individuals. To date, it is unclear whether there is a common gut microbial signature in patients with MS across studies. To identity the most common compositional differences of the gut microbiome in MS versus healthy controls, we performed a meta-analysis. This was based on 16S rRNA gene sequences from seven published studies, comprising a total of 524 adult patients with MS and control subjects. Results We found that although alpha and beta diversity did not differ between MS and controls, a lower relative abundance of Prevotella and a dysbiosis of numerous genera within the Clostridia class were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotellacorrelation in controls was disrupted in MS. immunosuppressive agents normalized MS-associated microbiome Prevotella to a similar level as healthy controls. Conclusions Our meta-analysis revealed reproducible gut microbiome signatures in MS across geographically diverse studies. These findings form the basis for future novel therapeutic approaches and possibly enhanced MS recognition/diagnosis by targeting common microbiome signatures.

Bone loss is common in sickle cell disease (SCD), but the molecular mechanisms is unclear. Serum insulin-like growth factor 1 (IGF1) was low in SCD subjects and SCD mice. To determine if decreased IGF1 associated with low bone mass in SCD is due to reduced SCFA production by gut microbiota, we performed reciprocal fecal microbiota transplantation (FMT) between healthy control (Ctrl) and SCD mice. uCT and histomorphometry analysis of femur showed decreased bone volume/total volume (BV/TV), trabecular number (Tb.N), osteoblast surface/bone surface (Ob.S/BS), mineralizing surface/ bone surface (MS/BS), inter-label thickness (Ir.L.Th) in SCD mice were significantly improved after receiving Ctrl feces. Bone formation genes Alp, Col1, Runx2, and Dmp1 from SCD mice were significantly decreased and were rescued after FMT from Ctrl feces. Transplantation of Ctrl feces increased the butyrate, valerate, and propionate levels in cecal content of SCD mice. Decreased G-coupled protein receptors 41 and 43 (GPR41 and GPR43) mRNA in tibia and lower IGF1 in bone and serum of SCD mice were partially restored after FMT from Ctrl feces. These data indicate that the healthy gut microbiota of Ctrl mice is protective for SCD bone loss through regulating IGF1 in response to impaired bacterial metabolites SCFAs.

Despite widely used preventive measures such as sealant programs to control caries prevalence, disparities are seen among ethnic groups. Supragingival plaque harbors hundreds of bacterial species, playing a significant role in oral health and disease. It is unknown whether the ethnic variation influences the supragingival microbiota in children. In our study, variations in microbiota of the supragingival plaque was investigated from 96 children between 6 and 11 years old in four ethnic groups (African American, Burmese, Caucasian, and Hispanic) from the same geographic location by 16S rRNA gene sequencing. We found that the microbial alpha and beta diversity of supragingival microbiota significantly differed between ethnic groups. The supragingival plaque microbiota had the most complex microbial community in Burmese children. Within-group microbiota similarity in Burmese or Caucasian children was significantly higher than between-groups similarity. We identified seven ethnic group-specific bacterial taxa after adjusting for dental plaque index, decayed missing filled teeth (DMFT) and the frequency of brushing. Children with high plaque index and high DMFT values were more similar to each other in the overall microbial community, compared to low plaque index or low DMFT groups in which inter-subject variation is high. Several bacterial taxa associated with high plaque index or high DMFT were ethnic group-specific. These results demonstrated that supragingival microbiota differed among ethnicity groups in children.

Summary: Background: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder. Methods: We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted UPLC-MS. A four-day food diary was recorded to capture the habitual dietary pattern of study participants. Findings: Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. The microbiome and metabolome profiles remained stable over six months in MS and control individuals. Interpretation: Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. Funding: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Background The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied. Methods In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months. Findings The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16+ dendritic cells in pwMS. Different mycobiome profiles, defined as mycotypes, were associated with different bacterial microbiome and immune cell subsets in the blood. Initial treatment with dimethyl fumarate, a common immunomodulatory therapy which also has fungicidal activity, did not cause uniform gut mycobiome changes across all pwMS. Interpretation There is an alteration of the gut mycobiome in pwMS, compared to healthy controls. Further study is required to assess any causal association of the mycobiome with MS and its direct or indirect interactions with bacteria and autoimmunity. Funding This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS102633-04 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-1805-31003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG- 1907-34474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

International audience; Increasing use of emerging per- and polyfluoroalkyl substances (PFASs) has caused extensive concerns around the world. Effective detection methods to trace their pollution characteristics and environmental behaviors in complex soil-crop systems are urgently needed. In this study, a reliable and matrix effect (ME)-free method was developed for simultaneous determination of 14 legacy and emerging PFASs, including perfluorooctanoic acid, perfluorooctane sulfonate, 6 hydrogenous PFASs, 3 chlorinated PFASs, and 3 hexafluoropropylene oxide homologues, in 6 crop (the edible parts) and 5 soil matrices using ultrasonic extraction combined with solid-phase extraction and ultraperformance liquid chromatography-mass spectrometry (MS)/MS. The varieties of extractants and cleanup cartridges, the dosage of ammonia hydroxide, and the ME were studied to obtain an optimal pretreatment procedure. The developed method had high sensitivity and accuracy with satisfactory method detection limits (2.40-83.03 pg/g dry weight) and recoveries (72-117%) of all target analytes in matrices at five concentrations, that is, 0.1, 1, 10, 100, and 1000 ng/g. In addition, the ME of this method (0.82-1.15) was negligible for all PFASs, even considering 11 different matrices. The successful application of the ME-free method to simultaneously determine the legacy and emerging PFASs in crop and soil samples has demonstrated its excellent practicability for monitoring emerging PFASs in soil-crop systems.

Necrotizing enterocolitis (NEC) is a devastating intestinal inflammatory disease of premature infants associated with gut bacterial dysbiosis. Using 16S rRNA-based methods, our laboratory identified an unclassified Enterobacteriaceae sequence (NEC_unk_OTU) with high abundance in NEC fecal samples. We aimed to identify this bacterium and determine its potential role in the disease. NCBI database searches for the 16S sequence, selective culture systems, biotyping and polymerase chain reaction were employed to refine classification of NEC_unk_OTU and identify toxin-encoding genes from the index NEC case. Bacterial cytotoxin production was confirmed by mass spectrometry and apoptosis assays. Additional fecal samples from 9 NEC and 5 non-NEC controls were analyzed using similar methods and multi-locus sequence typing (MLST) was performed to investigate clonal relationships and define sequence types of the isolates. NEC_unk_OTU was identified as Klebsiella oxytoca, a pathobiont known to cause antibiotic-associated hemorrhagic colitis, but not previously linked to NEC. Including the index case, cytotoxin-producing strains of K. oxytoca were isolated from 6 of 10 subjects with NEC; in these, the K. oxytoca 16S sequence predominated the fecal microbiota. Cytotoxin-producing strains of K. oxytoca also were isolated from 4 of 5 controls; in these, however, the abundance of the corresponding 16S sequence was very low. MLST analysis of the toxin-positive isolates demonstrated no clonal relationships and similar genetic clustering between cases and controls. These results suggest cytotoxin-producing strains of K. oxytoca colonize a substantial proportion of premature infants. Some, perhaps many, cases of NEC may be precipitated by outgrowth of this opportunistic pathogen.

Necrotizing enterocolitis (NEC) is a devastating intestinal inflammatory disease of premature infants associated with gut bacterial dysbiosis. Using 16S rRNA-based methods, our laboratory identified an unclassified Enterobacteriaceae sequence (NEC_unk_OTU) with high abundance in NEC fecal samples. We aimed to identify this bacterium and determine its potential role in the disease. NCBI database searches for the 16S sequence, selective culture systems, biotyping and polymerase chain reaction were employed to refine classification of NEC_unk_OTU and identify toxin-encoding genes from the index NEC case. Bacterial cytotoxin production was confirmed by mass spectrometry and apoptosis assays. Additional fecal samples from 9 NEC and 5 non-NEC controls were analyzed using similar methods and multi-locus sequence typing (MLST) was performed to investigate clonal relationships and define sequence types of the isolates. NEC_unk_OTU was identified as Klebsiella oxytoca, a pathobiont known to cause antibiotic-associated hemorrhagic colitis, but not previously linked to NEC. Including the index case, cytotoxin-producing strains of K. oxytoca were isolated from 6 of 10 subjects with NEC; in these, the K. oxytoca 16S sequence predominated the fecal microbiota. Cytotoxin-producing strains of K. oxytoca also were isolated from 4 of 5 controls; in these, however, the abundance of the corresponding 16S sequence was very low. MLST analysis of the toxin-positive isolates demonstrated no clonal relationships and similar genetic clustering between cases and controls. These results suggest cytotoxin-producing strains of K. oxytoca colonize a substantial proportion of premature infants. Some, perhaps many, cases of NEC may be precipitated by outgrowth of this opportunistic pathogen.

Microorganisms are used to alleviate heavy metal stress in plants cultivated in contaminated fields. However, the relevant mechanisms have been rarely explored. The goal of this study was to investigate effects of arbuscular mycorrhizal fungus

The large-scale use of quaternary ammonium compounds (QACs) in medicines or disinfectants can lead to their release into the environment, posing a potential risk to organisms. This study examined the effects of three typical QACs, dodecyltrimethylammonium chloride (DTAC), dodecyldimethylbenzylammonium chloride (DBAC), and didodecyldimethylammonium chloride (DDAC), on hydroponically cultured wheat seedlings. After 14 days of exposure, both hormesis and phytotoxicity were observed in the wheat seedlings. The shoot and root fresh weight gradually increased as QAC concentrations rose from 0.05 to 0.8 mg L-1. However, higher QAC concentrations severely inhibited plant growth by decreasing shoot and root fresh weight, total root length, and photosynthetic pigment content. Moreover, the increase in malondialdehyde and O-2(.-) contents, as well as root membrane permeability, reflected an oxidative burst and membrane lipid peroxidation caused by QACs. However, the effects of QACs on the levels of these oxidative stress markers were compound-specific, and the changes in superoxide dismutase, peroxidases, and catalase activity were partly related to reactive oxygen species levels. Considering the order of median effective concentration values (EC50) and the levels of oxidative stress induced by the three tested QACs, their phytotoxicities in wheat seedlings increased in the following order: DDAC < DTAC < DBAC, which mainly depended on their characteristics and applied concentrations. These results, which illustrated the complexity of QAC toxicity to plants, could potentially be used to assess the risk posed by these compounds in the environment.

Microorganisms are used to alleviate heavy metal stress in plants cultivated in contaminated fields. However, the relevant mechanisms have been rarely explored. The goal of this study was to investigate effects of arbuscular mycorrhizal fungus Funneliformis mosseae and two Cd-resistant bacterial strains (Enterobacter sp. EG16 and Enterobacter ludwigii DJ3) on growth and Cd tolerance of tomato when applied with different inoculation strategies (single or dual) and Cd concentrations (50 and 100 mg kg−1). Better plant growth was observed in mycorrhizal alone or combined treatments. In F. mosseae and EG16 co-inoculation treatment, shoot and root dry weight were 119–154% and 91–173% higher than those of the control, respectively. Higher bacterial and mycorrhizal colonization rate and root Cd concentration were also found in this treatment. However, the decrease of shoot Cd concentration and translocation factor values indicated this treatment was effective in improving Cd tolerance of the host plants. In addition, the increase in soil pH and decline in bioavailable Cd in the rhizosphere might be partly involved in reduction of Cd accumulation in plants. Our results suggest that co-inoculation with suitable microorganisms is important in plant growth and tolerance to Cd in Cd-contaminated soil.

Novel alternatives of perfluorooctane sulfonate (PFOS), chlorinated polyfluorinated ether sulfonates (Cl-PFAESs) are increasingly being detected in the aquatic and terrestrial environment. Previous studies mainly focused on aquatic biota; however, the knowledge about the ecotoxicological risk they pose to terrestrial plants was still lacking. In this study, the accumulation of two Cl-PFAES (6:2 and 8:2 Cl-PFAES) and PFOS in wheat seedlings at environmentally relevant levels (50 and 100 μg L−1) was investigated. Concentrations of Cl-PFAESs in the roots were an order of magnitude higher than those in shoots, indicating that they were primarily accumulated in the roots. The values of root and shoot bioconcentration factor was comparable between 6:2 Cl-PFAES and PFOS. However, these indexes of 8:2 Cl-PFAES were 42–91% higher and 70–76% lower than PFOS, respectively. As a result, 6:2 Cl-PFAES had a similar accumulation pattern as PFOS, whereas 8:2 Cl-PFAES was predominantly restricted to the roots, which might be attributed to their hydrophobicity and carbon chain length. In addition, at 250 mg L−1 of Cl-PFAESs, plant biomass and pigment content were 24–30% and 0.4–18%, respectively, which were lower than those of PFOS. As compared with PFOS, Cl-PFAESs induced higher levels of root membrane permeability, reactive oxygen species and malondialdehyde content, as well as reduced the activities of antioxidant enzymes and glutathione content. These suggested the occurrence of a severer oxidative damage and the breakdown of the antioxidant defence system in wheat cells. Therefore, we conclude that Cl-PFAESs might pose a higher potential threat to the environment than PFOS.

Phthalate acid esters (PAEs) are of particular concern due to their potential environmental risk to human and nonhuman organisms. Although uptake of PAEs by plants has been reported by several researchers, information about the intracellular distribution and uptake mechanisms of PAEs is still lacking. In this study, a series of hydroponic experiments using intact pumpkin (Cucurbita moschata) seedlings was conducted to investigate how di-n-butyl phthalate (DnBP), one of the most frequently identified PAEs in the environment, enters and is distributed in roots. DnBP was transported into subcellular tissues rapidly in the initial uptake period (

Siderophores, as strong chelators specific to iron, have been intensively studied in relation to the facilitation of biological iron acquisition from iron oxides. In this study, the dissolution of hematite in the presence of the siderophore desferrioxamine B (DFOB) and three low-molecular-weight organic acids (LMWOAs, i.e., oxalic, citric, or malic acid) was investigated at three pH conditions (3.0, 5.5, and 9.0). Hematite dissolution was pH-dependent and LMWOA-specific. The adsorption of DFOB on hematite was significantly higher at pH 9.0 than at the other pH values. The adsorption of oxalic acid on hematite, however, showed a descending trend as pH was increased, and adsorption of citric and malic acids was not significantly affected by pH. The Fourier transform infrared (FTIR) results also indicated the occurrence of these ligands’ adsorption. After acidification, dissolved iron was detected only in suspensions of hematite pre-adsorbed with oxalic acid at pH 5.5 and 9.0 or pre-adsorbed with citric acid at pH 5.5, indicating that these LMWOAs promoted the formation of labile iron on the hematite surface. Based on previous research and the results of this study, a hypothetical model is proposed. These results provide insight into the effect of LMWOAs on the dissolution of hematite promoted by DFOB.

Among the mathematical optimization algorithms, simplex algorithm is a popular and practical algorithm which was listed as one of the top 10 algorithms of the twentieth century by the journal Computing in Science and Engineering. Although simplex algorithm is efficient in the linear programming, the quality of convergence is unacceptable in practice as a numerical breakdown of the algorithm, even for smooth and well-behaved functions. On the other hand, full convergence might be seen in genetic algorithms (GA) using only crossover. So in this paper we combine the GA and simplex algorithm by initializing simplex from the final individual in GA and getting the converged result through simplex algorithm thereafter. A case study in estimating gas emission shows noteworthy improvement of efficiency and stability, compared with GA or simplex algorithm.

Uptake and accumulation by plants is a significant pathway in the migration and transformation of phthalate esters (PAEs) in the environment. However, limited information is available on the mechanisms of PAE metabolism in plants. Here, we investigated the metabolism of di-n-butyl phthalate (DnBP), one of the most frequently detected PAEs, in pumpkin (Cucurbita moschata) seedlings via a series of hydroponic experiments with an initial concentration of 10 mg L-1. DnBP hydrolysis occurred primarily in the root, and two of its metabolites, mono-n-butyl phthalate (MnBP) and phthalic acid (PA), were detected in all plant tissues. The MnBP concentration was an order of magnitude higher than that of PA in shoots, which indicated MnBP was more readily transported to the shoot than was PA because of the former's dual hydrophilic and lipophilic characteristics. More than 80% of MnBP and PA were located in the cell water-soluble component except that 96% of MnBP was distributed into the two solid cellular fractions (i.e., cell wall and organelles) at 96 h. A 13-20% and 29-54% increase of carboxylesterase (CXE) activity shown in time-dependent and concentration-dependent experiments, respectively, indicated the involvement of CXEs in plant metabolism of DnBP. The level of CXE activity in root subcellular fractions was in the order: the cell water-soluble component (88-94%) >> cell wall (3-7%) > cell organelles (3-4%), suggesting that the cell water-soluble component is the dominant locus of CXE activity and also the domain of CXE-catalyzed hydrolysis of DnBP. The addition of triphenyl phosphate, a CXE inhibitor, led to 43-56% inhibition of CXE activity and 16-25% increase of DnBP content, which demonstrated the involvement of CXEs in plant metabolism of DnBP. This study contributes to our understanding of enzymitic mechanisms of PAE transformation in plants.

Plant-associated bacteria are of great interest because of their potential use in phytoremediation. However, their ability to survive and promote plant growth in metal-polluted soils remains unclear. In this study, a soilborne Cd-resistant bacterium was isolated and identified as Enterobacter sp. strain EG16. It tolerates high external Cd concentrations (Cd 2+ MIC, >250 mg liter −1 ) and is able to produce siderophores and the plant hormone indole-3-acetic acid (IAA), both of which contribute to plant growth promotion. Surface biosorption in this strain accounted for 31% of the total Cd accumulated. The potential presence of cadmium sulfide, shown by energy-dispersive X-ray (EDX) analysis, suggested intracellular Cd binding as a Cd response mechanism of the isolate. Cd exposure resulted in global regulation at the transcriptomic level, with the bacterium switching to an energy-conserving mode by inhibiting energy-consuming processes while increasing the production of stress-related proteins. The stress response system included increased import of sulfur and iron, which become deficient under Cd stress, and the redirection of sulfur metabolism to the maintenance of intracellular glutathione levels in response to Cd toxicity. Increased production of siderophores, responding to Cd-induced Fe deficiency, not only is involved in the Cd stress response systems of EG16 but may also play an important role in promoting plant growth as well as alleviating the Cd-induced inhibition of IAA production. The newly isolated strain EG16 may be a suitable candidate for microbially assisted phytoremediation due to its high resistance to Cd and its Cd-induced siderophore production, which is likely to contribute to plant growth promotion.