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Annals of Translational Medicine Mar 2022The gut microbiome is associated with the response to immunotherapy in a variety of advanced cancers. However, the influence of the gut microbiome on locally advanced...
Crosstalk between the gut microbiome and clinical response in locally advanced thoracic esophageal squamous cell carcinoma during neoadjuvant camrelizumab and chemotherapy.
BACKGROUND
The gut microbiome is associated with the response to immunotherapy in a variety of advanced cancers. However, the influence of the gut microbiome on locally advanced esophageal squamous cell carcinoma (ESCC) during programmed cell death protein 1 (PD-1) antibody immunotherapy plus chemotherapy is not clearly demonstrated. To explore the crosstalk between the gut microbiome and clinical response in locally advanced thoracic ESCC during neoadjuvant camrelizumab and chemotherapy.
METHODS
Patients who were diagnosed with locally advanced thoracic ESCC and had not received treatment were enrolled. The treatment regimen was two cycles of camrelizumab combined with carboplatin and albumin paclitaxel before surgery. The research endpoints were pathological complete response (pCR) and major pathological response (MPR). Fecal samples were collected at three time points: before neoadjuvant therapy, after two cycles of neoadjuvant therapy, and after surgery. We performed 16S ribosomal ribonucleic acid (rRNA) V3-V4 sequencing of the gene amplicons of fecal samples, as well as bacterial diversity and differential abundance analyses.
RESULTS
A total of 46 patients were recruited, and 44, 42, and 35 fecal samples were collected at the three time points, respectively. Statistically significant differences were observed in the amplicon sequence variant (ASV)-level alpha diversity indices, including Chao1, Shannon, and Good's coverage, between the three time points. The non-pCR-enriched gut microbiota included Proteobacteria, Dialister, Aeromonadales, Pseudomonadales, Thermi, Deinococci, Moraxellaceae, Rhodocyclales, Rhodocyclaceae, and Acinetobacter. The non-MPR-enriched gut microbiota included Pseudomonadales and the mitochondria family. The MPR-enriched gut microbiota included the Barnesiellaceae, Pyramidobacter, Dethiosulfovibrionaceae, Odoribacteraceae, Butyricimonas, Prevotella, Barnesiella, and Odoribacter. Patients with ≥3 grade adverse events (AEs) exhibited enrichment in the Succiniclasticum, Nakamurella, Rhizobium, Granulicella, Phyllobacteriaceae, Pelagibacteraceae, Actinosynnemataceae, Aquirestis, Flavisolibacter, Chelativorans, Coxiellaceae Acidicapsa, Acidobacteriaceae, Lentzea, Staphylococcus, Plesiomonas, Dysgonomonas, Pseudonocardia, and Ellin6075.
CONCLUSIONS
We found that the diversity of the gut microbiome declined after neoadjuvant PD-1 antibody immunotherapy plus chemotherapy and surgery. Patients with pCR had different types and proportions of gut microbiota before treatment compared to those without pCR. We also observed the difference between patients with or without ≥ grade 3 AEs. The taxonomic features of the gut microbiome are potential biomarkers that could predict the pathological response and AEs.
PubMed: 35433940
DOI: 10.21037/atm-22-1165 -
Scientific Reports Jun 2022Tamarindus indica is one of the tropical medicinal plants that has been attributed curative potential of numerous diseases by many rural dwellers. This study was...
Tamarindus indica is one of the tropical medicinal plants that has been attributed curative potential of numerous diseases by many rural dwellers. This study was designed to evaluate the antioxidant, antibacterial activities and also to determine the various chemical constituents responsible for its pharmacological activities. The methanol extract of Tamarindus indica fruit pulp was analyzed by Gas Chromatography/Mass Spectrometer to determine the volatile compounds present. The antioxidant activities were performed using DPPH and FRAP method and the antibacterial activity was tested against some common pathogens by macro broth dilution method. The GCMS analysis shows the presence of 37 compounds, out of which 14 had their peak area percentages ≥ 1% and only two compounds had no reported pharmacological activities. Most of the bioactive compounds including 5-Hydroxymethylfurfural (31.06%)-3-O-Methyl-d-glucose (16.31%), 1,6-anhydro-β-D-Glucopyranose (9.95%), 5-methyl-Furancarboxaldehyde (3.2%), Triethylenediamine (1.17%), 1-(2-furanyl)-1-Propcanone (2.18%), Methyl 2-furoate (3.14%), Levoglucosenone (3.21%), methyl ester-Hepta-2,4-dienoic acid, (8.85%), 2,3-dihydro-3,5-dihydrox-4H-Pyran-4-one (3.4%), O-α-D-glucopyranosyl-(1.fwdarw.3)-β-D-fructofuranosyl-α-D-Glucopyranoside (2.18%), n-Hexadecanoic acid (1.38%), 2-Heptanol, acetate (1.29%), 5-[(5-methyl-2-fur-2-Furancarboxaldehyde (1.08%), 3-Methyl-2-furoic acid (1.05%) and cis-Vaccenic acid (2.85%)have been reported with different activities such as antibacterial, antifungal, antitubercular, anticancer, antioxidant and other prophylactic activities. The extract demonstrated inhibitory potential against all tested pathogen. However, Plesiomonas shigellosis ATCC 15903 and Bacillus pumillus ATCC 14884 are more sensitive with the MIC of 0.22 and 0.44 mg/ml respectively. The antioxidant activity was relatively low due to the low phenolic content of the extract. This shows that there is a strong correlation between antioxidant activities and phenolic content. GC-MS analysis revealed the presence of bioactive phytoconstituents with various biological activities and this justifies the rationale behind its usage as a curative therapy by many local dwellers.
Topics: Anti-Bacterial Agents; Antioxidants; Methanol; Phenols; Plant Extracts; Tamarindus
PubMed: 35676439
DOI: 10.1038/s41598-022-13716-x -
Environment International Aug 2022Perfluorooctane sulfonate (PFOS) has been reported to induce hepatotoxicity in wildlife and humans. Novel PFOS alternatives have been widely used following restrictions...
Perfluorooctane sulfonate (PFOS) has been reported to induce hepatotoxicity in wildlife and humans. Novel PFOS alternatives have been widely used following restrictions on PFOS, but little is known about their potential toxicity. Here, the first comprehensive investigation on the chronic hepatotoxicity and underlying molecular mechanisms of PFOS, 6:2Cl-PFESA (F-53B), and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) was carried out on adult zebrafish through a histopathological examination, biochemical measurement, and multi-omics analysis. PFOS and its alternatives caused changes in liver histopathology and liver function indices in the order of F-53B > PFOS > OBS, which was consistent with their concentration in the liver. In silico modeling and transcriptional profiles suggested that the aberrant hepatic lipid metabolism induced by F-53B and PFOS was initiated by the action on peroxisome proliferator-activated receptor γ (PPARγ), which triggered changes in downstream genes transcription and led to an imbalance between lipid synthesis and expenditure. Gut microbiome analysis provided another novel mechanistic perspective that changes in the abundance of Legionella, Ralstonia, Brevundimonas, Alphaproteobacteria, Plesiomonas, and Hyphomicrobium might link to alterations in the PPAR pathway based on their significant correlation. This study provides insight into the molecular mechanisms of hepatotoxicity induced by PFOS and its novel alternatives and highlights the need for concern about their environmental exposure risks.
PubMed: 35738203
DOI: 10.1016/j.envint.2022.107351 -
Vaccines Nov 2022The swift emergence of antibiotic resistance (AR) in bacterial pathogens to make themselves adaptable to changing environments has become an alarming health issue. To...
The swift emergence of antibiotic resistance (AR) in bacterial pathogens to make themselves adaptable to changing environments has become an alarming health issue. To prevent AR infection, many ways can be accomplished such as by decreasing the misuse of antibiotics in human and animal medicine. Among these AR bacterial species, is one of the etiological agents of intestinal infection in humans. It is a gram-negative rod-shaped bacterium that is highly resistant to several classes of antibiotics, and no licensed vaccine against the aforementioned pathogen is available. Hence, substantial efforts are required to screen protective antigens from the pathogen whole genome that can be subjected easily to experimental evaluations. Here, we employed a reverse vaccinology (RV) approach to design a multi-antigenic epitopes based vaccine against . The complete genomes of were retrieved from the National Center for Biotechnological Information (NCBI) that on average consist of 5226 proteins. The complete proteomes were subjected to different subtractive proteomics filters, and in the results of that analysis, out of total proteins, 2399 were revealed as non-redundant and 2827 as redundant proteins. The non-redundant proteins were further checked for subcellular localization analysis, in which three were localized in the extracellular matrix, eight were outer membrane, and 13 were found in the periplasmic membrane. All surface localized proteins were found to be virulent. Out of a total of 24 virulent proteins, three proteins (flagellar hook protein (FlgE), hypothetical protein, and TonB-dependent hemoglobin/transferrin/lactoferrin family receptor protein) were considered as potential vaccine targets and subjected to epitopes prediction. The predicted epitopes were further examined for antigenicity, toxicity, and solubility. A total of 10 epitopes were selected (GFKESRAEF, VQVPTEAGQ, KINENGVVV, ENKALSQET, QGYASANDE, RLNPTDSRW, TLDYRLNPT, RVTKKQSDK, GEREGKNRP, RDKKTNQPL). The selected epitopes were linked with each other via specific GPGPG linkers in order to design a multi-epitopes vaccine construct, and linked with cholera toxin B subunit adjuvant to make the designed vaccine construct more efficient in terms of antigenicity. The 3D structure of the vaccine construct was modeled ab initio as no appropriate template was available. Furthermore, molecular docking was carried out to check the interaction affinity of the designed vaccine with major histocompatibility complex (MHC-)I (PDB ID: 1L1Y), MHC-II (1KG0), and toll-like receptor 4 ((TLR-4) (PDB: 4G8A). Molecular dynamic simulation was applied to evaluate the dynamic behavior of vaccine-receptor complexes. Lastly, the binding free energies of the vaccine with receptors were estimated by using MMPB/GBSA methods. All of the aforementioned analyses concluded that the designed vaccine molecule as a good candidate to be used in experimental studies to disclose its immune protective efficacy in animal models.
PubMed: 36366394
DOI: 10.3390/vaccines10111886 -
Frontiers in Microbiology 2023As a catadromous fish, Asian sea bass () juveniles migrate from seawater (SW) to freshwater (FW) for growth and development. During migration, they undergo physiological...
As a catadromous fish, Asian sea bass () juveniles migrate from seawater (SW) to freshwater (FW) for growth and development. During migration, they undergo physiological changes to acclimate to environmental salinity. Thus, it is crucial to understand how SW-to-FW migration affects the gut microbiota of catadromous fish. To the best of our knowledge, no study has revealed the effects of transfer to hypotonic environments on a catadromous fish microbiota. In this study, we aimed to determine the effects of FW transfer on the microbiota and cytokine gene expression in the intestines of juvenile catadromous Asian sea bass. The relationship between the water and the gut microbiota of this euryhaline species was also examined. We found that FW transfer affected both mucosa- and digesta-associated microbiota of Asian sea bass. and were dominant in both the mucosa- and digesta-associated microbiota of FW-acclimated sea bass. The pathogenic genera , s, and were dominant in the SW group. Although dominant fish microbes were present in the water, fish had their own unique microbes. Vitamin B6 metabolism was highly expressed in the FW fish microbiota, whereas arginine, proline, and lipid metabolism were highly expressed in the SW fish microbiota. Additionally, the correlation between cytokine gene expression and microbiota was found to be affected by FW transfer. Taken together, our results demonstrated that FW transfer altered the composition and functions of mucosa- and digesta-associated microbiota of catadromous Asian sea bass intestines, which correlated with cytokine gene expression.
PubMed: 37089546
DOI: 10.3389/fmicb.2023.1097954 -
Journal of Medical Case Reports Jan 2022The detection of epidemic-prone pathogens is important in strengthening global health security. Effective public health laboratories are critical for reliable, accurate,...
Surveillance and laboratory collaboration in response to an outbreak of Vibrio parahaemolyticus, Plesiomonas shigelloides, and Aeromonas hydrophila in Sekondi-Takoradi, Ghana: a case series.
BACKGROUND
The detection of epidemic-prone pathogens is important in strengthening global health security. Effective public health laboratories are critical for reliable, accurate, and timely testing results in outbreak situations. Ghana received funding as one of the high-risk non-Ebola affected countries to build and strengthen public health infrastructure to meet International Health Regulation core capacities. A key objective was to build laboratory capacities to detect epidemic-prone diseases.
CASE PRESENTATION
In June 2018, a local hospital received eight patients who presented with acute diarrhea. A sample referral system for Ghana has not been established, but the Sekondi Zonal Public Health Laboratory staff and mentors collaborated with Disease Surveillance Officers (DSOs) to collect, package, and transport stool specimens from the outbreak hospital to the Public Health Laboratory for laboratory testing. The patients included seven females and one male, of Fante ethnicity from the Fijai township of Sekondi-Takoradi Municipality. The median age of the patients was 20 years (interquartile range: 20-29 years). Vibrio parahaemolyticus was identified within 48 hours from four patients, Plesiomonas shigelloides from one patient, and Aeromonas hydrophila from another patient. There was no bacteria growth from the samples from the two other patients. All patients were successfully treated and discharged.
CONCLUSION
This is the first time these isolates have been identified at the Sekondi Zonal Public Health Laboratory, demonstrating how rapid response, specimen transportation, laboratory resourcing, and public health coordination are important in building capacity towards achieving health security. This capacity building was part of the United States Centers for Disease Control and Prevention engagement of international and local partners to support public health laboratories with supplies, diagnostic equipment, reagents, and logistics.
Topics: Adult; Aeromonas; Aeromonas hydrophila; Disease Outbreaks; Ghana; Humans; Laboratories; Male; Plesiomonas; Vibrio parahaemolyticus; Young Adult
PubMed: 35086562
DOI: 10.1186/s13256-021-03243-0 -
Microbiology Spectrum Jun 2023Poplar anthracnose caused by Colletotrichum gloeosporioides is a common disease affecting poplars globally that causes the destruction and alteration of poplar...
Poplar anthracnose caused by Colletotrichum gloeosporioides is a common disease affecting poplars globally that causes the destruction and alteration of poplar phyllosphere microbial communities; however, few studies have investigated these communities. Therefore, in this study, three species of poplar with different resistances were investigated to explore the effects of and poplar secondary metabolites on the composition of poplar phyllosphere microbial communities. Evaluation of the phyllosphere microbial communities before and after inoculation of the poplars with revealed that both bacterial and fungal OTUs decreased after inoculation. Among bacteria, the most abundant genera were , , Pseudomonas, , , Streptococcus, , and for all poplar species. Among fungi, the most abundant genera before inoculation were , Aspergillus, Fusarium, , and , while was the main genus after inoculation. The inoculation of pathogens may regulate the phyllosphere microorganisms by affecting the secondary metabolites of plants. We investigated metabolite contents in the phyllosphere before and after the inoculation of the three poplar species, as well as the effects of flavonoids, organic acids, coumarins, and indoles on poplar phyllosphere microbial communities. We speculated that coumarin had the greatest recruitment effect on phyllosphere microorganisms, followed by organic acids through regression analysis. Overall, our results provide a foundation for subsequent screening of antagonistic bacteria and fungi against poplar anthracnose and investigations of the mechanism by which poplar phyllosphere microorganisms are recruited. Our findings revealed that the inoculation of has a greater effect on the fungal community than the bacterial community. In addition, coumarins, organic acids, and flavonoids may have recruitment effects on phyllosphere microorganisms, while indoles may have inhibitory effects on these organisms. These findings may provide the theoretical basis for the prevention and control of poplar anthracnose.
Topics: Colletotrichum; Bacteria; Bacillus; Microbiota; Plant Diseases
PubMed: 37219434
DOI: 10.1128/spectrum.04603-22 -
BMC Veterinary Research Apr 2022Bacterial infections are responsible of high economic losses in aquaculture. Mexican golden trout (Oncorhynchus chrysogaster) is a threatened native trout species that...
Bacterial and parasite co-infection in Mexican golden trout (Oncorhynchus chrysogaster) by Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator.
BACKGROUND
Bacterial infections are responsible of high economic losses in aquaculture. Mexican golden trout (Oncorhynchus chrysogaster) is a threatened native trout species that has been introduced in aquaculture both for species conservation and breeding for production and for which no studies of bacterial infections have been reported.
CASE PRESENTATION
Fish from juvenile stages of Mexican golden trout showed an infectious outbreak in a farm in co-culture with rainbow trout (Oncorhynchus mykiss), showing external puntiform red lesions around the mouth and caudal pedunculus resembling furuncles by Aeromonas spp. and causing an accumulated mortality of 91%. Isolation and molecular identification of bacteria from lesions and internal organs showed the presence of Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator isolated from a single individual. All bacterial isolates were resistant to amoxicillin-clavulanic acid and cefazoline. P. shigelloides was resistant to third generation β-lactamics.
CONCLUSIONS
This is the first report of coinfection by Aeromonas bestiarum, Aeromonas sobria, Plesiomonas shigelloides and Ichthyobodo necator in an individual of Mexican golden trout in co-culture with rainbow trout. Resistance to β-lactams suggests the acquisition of genetic determinants from water contamination by human- or livestock-associated activities.
Topics: Aeromonas; Animals; Coinfection; Fish Diseases; Gram-Negative Bacterial Infections; Necator; Oncorhynchus; Oncorhynchus mykiss; Parasites; Plesiomonas
PubMed: 35414073
DOI: 10.1186/s12917-022-03208-5 -
Frontiers in Nutrition 2022Varying dietary inclusion levels of fish protein hydrolysates (FPH) were applied in a feeding experiment with juvenile largemouth bass () to assess their effects on...
Varying dietary inclusion levels of fish protein hydrolysates (FPH) were applied in a feeding experiment with juvenile largemouth bass () to assess their effects on growth, intestinal antioxidant status, immunity, and microflora. FPH were added in 4 dietary levels: 0 g/kg (control group, FPH-0), 10 g/kg (FPH-10), 30 g/kg (FPH-30), and 50 g/kg (FPH-50) dry matter, respectively substituting 0, 5.3, 16.3, and 27.3% of fish meal with dietary fish meal. Quadruplicate groups of 25 juvenile largemouth bass with initial body weight 9.51 ± 0.03 g were fed during the 56-day feeding experiment. Experimental results showed that fish fed FPH-30 obtained a significantly higher weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), and significant feed conversion rate (FCR) compared to the other three groups ( < 0.05). FPH-30 group also promoted protein synthesis and deposition, as evidenced by the higher whole-body crude protein contents, the higher expressions of GH1, IGF-1, TOR, and S6K in the liver, and SLC7A5, SLC7A8, SLC38A2, and SLC15A2 in the intestine than the other three groups. FPH-30 group could also enhance intestinal health status by increasing the activities of SOD, POD, CAT, GSH-Px, and T-AOC activities by upregulating the expressions of SOD, GSH-Px, IL1β, and TNFβ, and by reducing the MDA contents and the expressions of IL15, Caspase 3, Caspase 9, and Caspase 10 than other groups. Compared to the control group, the abundance markedly decreased in FPH treatments, while the variation tendency of the phylum was opposite. The peak value of ratio and the lowest of abundance were seen in largemouth bass fed FPH-30 ( < 0.05). Fish in three FPH treatments had lower abundances of opportunistic pathogens and than fish in the control group. In conclusion, FPH is a nutritious feed ingredient for juvenile largemouth bass, and can be added to a dietary level of 30 g/kg dry matter replacing fish meal without any negative effect on growth and feed utilization. FPH supplements could also strengthen the intestinal immune mechanisms of largemouth bass to tackle the immunodeficiency produced by fish meal replacement.
PubMed: 35634365
DOI: 10.3389/fnut.2022.816341 -
Frontiers in Immunology 2022The present study was conducted to investigate the effects of dietary inclusion of protein hydrolysates on growth performance, digestive enzyme activities, protein...
The present study was conducted to investigate the effects of dietary inclusion of protein hydrolysates on growth performance, digestive enzyme activities, protein metabolism, and intestinal health in larval largemouth bass (). The experimental feeding trial presented in this study was based on five isonitrogenous and isolipidic diets formulated with graded inclusion levels of protein hydrolysates, and it showed that protein hydrolysates improved growth performance, reduced larval deformity rate, and increased the activity of digestive enzymes, including pepsin and trypsin. Gene expression results revealed that the supplementation of protein hydrolysates upregulated the expression of intestinal amino acid transporters LAT2 and peptide transporter 2 (PepT2), as well as the amino acid transporters LAT1 in muscle. Dietary provision of protein hydrolysates activated the target of rapamycin (TOR) pathway including the up-regulation of TOR and AKT1, and down-regulation of 4EBP1. Additionally, the expression of genes involved in the amino acids response (AAR) pathway, ATF4 and REDD1, were inhibited. Protein hydrolysates inhibited the transcription of some pro-inflammatory cytokines, including IL-8 and 5-LOX, but promoted the expression of anti-inflammatory cytokines TGF-β and IL-10. The 16S rRNA analysis, using V3-V4 region, indicated that dietary protein hydrolysates supplementation reduced the diversity of the intestine microbial community, increased the enrichment of and reduced the enrichment of at the genus level. In summary, protein hydrolysates have been shown to be an active and useful supplement to positively complement other protein sources in the diets for largemouth bass larvae, and this study provided novel insights on the beneficial roles and possible mechanisms of action of dietary protein hydrolysates in improving the overall performance of fish larvae.
Topics: Animal Feed; Animals; Bass; Cytokines; Gastrointestinal Microbiome; Intestines; Larva; Protein Hydrolysates; RNA, Ribosomal, 16S
PubMed: 35928824
DOI: 10.3389/fimmu.2022.913024