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Applied and Environmental Microbiology May 2023Syntrophic propionate oxidation is one of the rate-limiting steps during anaerobic decomposition of organic matter in anoxic environments. Syntrophic... (Review)
Review
Syntrophic propionate oxidation is one of the rate-limiting steps during anaerobic decomposition of organic matter in anoxic environments. Syntrophic propionate-oxidizing bacteria (SPOB) are members of the "rare biosphere" living at the edge of the thermodynamic limit in most natural habitats. Hitherto, only 10 bacterial species capable of syntrophic propionate oxidization have been identified. SPOB employ different metabolisms for propionate oxidation (e.g., methylmalonyl-CoA pathway and C dismutation pathway) and show diverse life strategies (e.g., obligately and facultatively syntrophic lifestyle). The flavin-based electron bifurcation/confurcation (FBEB/C) systems have been proposed to help solve the thermodynamic dilemma during the formation of the low-potential products H and formate. Molecular ecological approaches, such as DNA stable isotope probing (DNA-SIP) and metagenomics, have been used to detect SPOB in natural environments. Furthermore, the biogeographical pattern of SPOB has been recently described in paddy soils. A comprehensive understanding of SPOB is essential for better predicting and managing organic matter decomposition and carbon cycling in anoxic environments. In this review, we described the critical role of syntrophic propionate oxidation in anaerobic decomposition of organic matter, phylogenetic and metabolic diversity, life strategies and ecophysiology, composition of syntrophic partners, and pattern of biogeographic distribution of SPOB in natural environments. We ended up with a few perspectives for future research.
Topics: Propionates; Phylogeny; Oxidation-Reduction; Bacteria; DNA; Methane; Anaerobiosis
PubMed: 37097179
DOI: 10.1128/aem.00384-23 -
Journal of Neuroinflammation Mar 2023Although the advent of combination anti-retroviral therapy (cART) has transformed HIV into a manageable chronic disease, an estimated 30-50% of people living with HIV...
Cannabinoids modulate the microbiota-gut-brain axis in HIV/SIV infection by reducing neuroinflammation and dysbiosis while concurrently elevating endocannabinoid and indole-3-propionate levels.
BACKGROUND
Although the advent of combination anti-retroviral therapy (cART) has transformed HIV into a manageable chronic disease, an estimated 30-50% of people living with HIV (PLWH) exhibit cognitive and motor deficits collectively known as HIV-associated neurocognitive disorders (HAND). A key driver of HAND neuropathology is chronic neuroinflammation, where proinflammatory mediators produced by activated microglia and macrophages are thought to inflict neuronal injury and loss. Moreover, the dysregulation of the microbiota-gut-brain axis (MGBA) in PLWH, consequent to gastrointestinal dysfunction and dysbiosis, can lead to neuroinflammation and persistent cognitive impairment, which underscores the need for new interventions.
METHODS
We performed RNA-seq and microRNA profiling in basal ganglia (BG), metabolomics (plasma) and shotgun metagenomic sequencing (colon contents) in uninfected and SIV-infected rhesus macaques (RMs) administered vehicle (VEH/SIV) or delta-9-tetrahydrocannabinol (THC) (THC/SIV).
RESULTS
Long-term, low-dose THC reduced neuroinflammation and dysbiosis and significantly increased plasma endocannabinoid, endocannabinoid-like, glycerophospholipid and indole-3-propionate levels in chronically SIV-infected RMs. Chronic THC potently blocked the upregulation of genes associated with type-I interferon responses (NLRC5, CCL2, CXCL10, IRF1, IRF7, STAT2, BST2), excitotoxicity (SLC7A11), and enhanced protein expression of WFS1 (endoplasmic reticulum stress) and CRYM (oxidative stress) in BG. Additionally, THC successfully countered miR-142-3p-mediated suppression of WFS1 protein expression via a cannabinoid receptor-1-mediated mechanism in HCN2 neuronal cells. Most importantly, THC significantly increased the relative abundance of Firmicutes and Clostridia including indole-3-propionate (C. botulinum, C. paraputrificum, and C. cadaveris) and butyrate (C. butyricum, Faecalibacterium prausnitzii and Butyricicoccus pullicaecorum) producers in colonic contents.
CONCLUSION
This study demonstrates the potential of long-term, low-dose THC to positively modulate the MGBA by reducing neuroinflammation, enhancing endocannabinoid levels and promoting the growth of gut bacterial species that produce neuroprotective metabolites, like indole-3-propionate. The findings from this study may benefit not only PLWH on cART, but also those with no access to cART and more importantly, those who fail to suppress the virus under cART.
Topics: Animals; Cannabinoids; Simian Acquired Immunodeficiency Syndrome; Endocannabinoids; Simian Immunodeficiency Virus; Propionates; Dronabinol; Neuroinflammatory Diseases; Brain-Gut Axis; Macaca mulatta; Dysbiosis; HIV Infections
PubMed: 36890518
DOI: 10.1186/s12974-023-02729-6 -
Journal of Pharmacological and... 2022The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of...
The 2021 Annual Safety Pharmacology (SP) Society (SPS) meeting was held virtually October 4-8, 2021 due to the continuing COVID-19 global pandemic. This themed issue of J Pharmacol Toxicol Methods comprises articles arising from the meeting. As in previous years the manuscripts reflect various areas of innovation in SP including a perspective on aging and its impact on drug attrition during safety assessments, an integrated assessment of respiratory, cardiovascular and animal activity of in vivo nonclinical studies, development of a dynamic QT-rate correction method in primates, evaluation of the "comprehensive in vitro proarrhythmia assay" (CiPA) ion channel protocol to the automated patch clamp, and best practices regarding the conduct of hERG electrophysiology studies and an analysis of secondary pharmacology assays by the FDA. The meeting also generated 85 abstracts (reproduced in the current volume of J Pharmacol Toxicol Methods). It appears that the validation of methods remains a challenge in SP. Nevertheless, the continued efforts to mine approaches to detection of proarrhythmia liability remains a baffling obsession given the ability of Industry to completely prevent drugs entering into clinical study only to be found to have proarrhythmic properties, with no reports of such for at least ten years. Perhaps it is time to move on from CiPA and find genuine problems to solve?
Topics: Animals; COVID-19; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Indoles; Ion Channels; Propionates
PubMed: 35926772
DOI: 10.1016/j.vascn.2022.107206 -
Nutrients Mar 2023Prebiotics are substrates that are selectively utilized by host microorganisms, thus conferring a health benefit. There is a growing awareness that interpersonal and...
Prebiotics are substrates that are selectively utilized by host microorganisms, thus conferring a health benefit. There is a growing awareness that interpersonal and age-dependent differences in gut microbiota composition impact prebiotic effects. Due to the interest in using human milk oligosaccharides (HMOs) beyond infancy, this study evaluated how HMOs [2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), 6'Sialyllactose (6'SL)] and blends thereof affect the microbiota of 6-year-old children ( = 6) and adults ( = 6), compared to prebiotics inulin (IN) and fructooligosaccharides (FOS). The ex vivo SIFR technology was used, given its demonstrated predictivity in clinical findings. First, HMOs and HMO blends seemed to maintain a higher α-diversity compared to FOS/IN. Further, while 2'FL/LNnT were bifidogenic for both age groups, 3'SL/6'SL and FOS/IN were exclusively bifidogenic for children and adults, respectively. This originated from age-related differences in microbiota composition because while 3'SL/6'SL stimulated (abundant in children), FOS/IN enhanced (abundant in adults). Moreover, all treatments significantly increased acetate, propionate and butyrate (only in adults) with product- and age-dependent differences. Among the HMOs, 6'SL specifically stimulated propionate (linked to in children and in adults), while LNnT stimulated butyrate (linked to in adults). Indole-3-lactic acid and 3-phenyllactic acid (linked to immune health) and gamma-aminobutyric acid (linked to gut-brain axis) were most profoundly stimulated by 2'FL and HMO blends in both children and adults, correlating with specific . Finally, 2'FL/LNnT increased melatonin in children, while 3'SL remarkably increased folic acid in adults. Overall, age-dependent differences in microbiota composition greatly impacted prebiotic outcomes, advocating for the development of age-specific nutritional supplements. HMOs were shown to be promising modulators in the adult, and particularly the children's microbiota. The observed HMO-specific effects, likely originating from their structural heterogeneity, suggest that blends of different HMOs could maximize treatment effects.
Topics: Adult; Humans; Child; Milk, Human; Bifidobacterium; Gastrointestinal Microbiome; Prebiotics; Propionates; Oligosaccharides; Inulin; Butyrates
PubMed: 37049541
DOI: 10.3390/nu15071701 -
Applied Microbiology and Biotechnology Jan 2018Bacteria from the Propionibacterium genus consists of two principal groups: cutaneous and classical. Cutaneous Propionibacterium are considered primary pathogens to... (Review)
Review
Bacteria from the Propionibacterium genus consists of two principal groups: cutaneous and classical. Cutaneous Propionibacterium are considered primary pathogens to humans, whereas classical Propionibacterium are widely used in the food and pharmaceutical industries. Bacteria from the Propionibacterium genus are capable of synthesizing numerous valuable compounds with a wide industrial usage. Biomass of the bacteria from the Propionibacterium genus constitutes sources of vitamins from the B group, including B12, trehalose, and numerous bacteriocins. These bacteria are also capable of synthesizing organic acids such as propionic acid and acetic acid. Because of GRAS status and their health-promoting characteristics, bacteria from the Propionibacterium genus and their metabolites (propionic acid, vitamin B12, and trehalose) are commonly used in the cosmetic, pharmaceutical, food, and other industries. They are also used as additives in fodders for livestock. In this review, we present the major species of Propionibacterium and their properties and provide an overview of their functions and applications. This review also presents current literature concerned with the possibilities of using Propionibacterium spp. to obtain valuable metabolites. It also presents the biosynthetic pathways as well as the impact of the genetic and environmental factors on the efficiency of their production.
Topics: Bacteriocins; Biomass; Biosynthetic Pathways; Fermentation; Industrial Microbiology; Propionates; Propionibacterium; Trehalose; Vitamin B 12
PubMed: 29167919
DOI: 10.1007/s00253-017-8616-7 -
ACS Synthetic Biology Jun 2023Short-chain fatty acids (SCFAs) are commonly found in the large intestine, but generally not in the small intestine, and influence microbiome composition and host...
Short-chain fatty acids (SCFAs) are commonly found in the large intestine, but generally not in the small intestine, and influence microbiome composition and host physiology. Thus, synthetic biologists are interested in developing engineered probiotics capable of detection of SCFAs as biogeography or disease sensors. One SCFA, propionate, is both sensed and consumed by . Here, we utilize the transcription factor PrpR, sensitive to the propionate-derived metabolite (2,3)-2-methylcitrate, and its cognate promoter P to detect extracellular propionate with the probiotic chassis bacterium Nissle 1917. We identify that PrpR-P displays stationary phase leakiness and transient bimodality, and we explain these observations through evolutionary rationales and deterministic modeling, respectively. Our results will help researchers build biogeographically sensitive genetic circuits.
Topics: Propionates; Escherichia coli; Transcription Factors; Microbiota; Promoter Regions, Genetic
PubMed: 37220256
DOI: 10.1021/acssynbio.3c00138 -
Journal of Dental Research May 2023Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are common chronic inflammatory conditions, manifesting as painful oral lesions that negatively affect...
Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are common chronic inflammatory conditions, manifesting as painful oral lesions that negatively affect patients' quality of life. Current treatment approaches are mainly palliative and often ineffective due to inadequate contact time of the therapeutic agent with the lesions. Here, we developed the Dental Tough Adhesive (DenTAl), a bioinspired adhesive patch with robust mechanical properties, capable of strong adhesion against diverse wet and dynamically moving intraoral tissues, and extended drug delivery of clobetasol-17-propionate, a first-line drug for treating OLP and RAS. DenTAl was found to have superior physical and adhesive properties compared to existing oral technologies, with ~2 to 100× adhesion to porcine keratinized gingiva and ~3 to 15× stretchability. Clobetasol-17-propionate incorporated into the DenTAl was released in a tunable sustained manner for at least 3 wk and demonstrated immunomodulatory capabilities , evidenced by reductions in several cytokines, including TNF-α, IL-6, IL-10, MCP-5, MIP-2, and TIMP-1. Our findings suggest that DenTAl may be a promising device for intraoral delivery of small-molecule drugs applicable to the management of painful oral lesions associated with chronic inflammatory conditions.
Topics: Animals; Swine; Clobetasol; Hydrogels; Quality of Life; Propionates; Dental Cements; Chronic Disease; Lichen Planus, Oral
PubMed: 36883653
DOI: 10.1177/00220345221148684 -
Molecular Nutrition & Food Research Sep 2022The gut microbiota plays a prominent role in gut-brain interactions and gut dysbiosis is involved in neuroinflammation. However, specific probiotics targeting...
SCOPE
The gut microbiota plays a prominent role in gut-brain interactions and gut dysbiosis is involved in neuroinflammation. However, specific probiotics targeting neuroinflammation need to be explored. In this study, the antineuroinflammatory effect of the potential probiotic Roseburia hominis (R. hominis) and its underlying mechanisms is investigated.
METHODS AND RESULTS
First, germ-free (GF) rats are orally treated with R. hominis. Microglial activation, proinflammatory cytokines, levels of short-chain fatty acids, depressive behaviors, and visceral sensitivity are assessed. Second, GF rats are treated with propionate or butyrate, and microglial activation, proinflammatory cytokines, histone deacetylase 1 (HDAC1), and histone H3 acetyl K9 (Ac-H3K9) are analyzed. The results show that R. hominis administration inhibits microglial activation, reduces the levels of IL-1α, INF-γ, and MCP-1 in the brain, and alleviates depressive behaviors and visceral hypersensitivity in GF rats. Moreover, the serum levels of propionate and butyrate are increased significantly in the R. hominis-treated group. Propionate or butyrate treatment reduces microglial activation, the levels of proinflammatory cytokines and HDAC1, and promotes the expression of Ac-H3K9 in the brain.
CONCLUSION
These findings suggest that R. hominis alleviates neuroinflammation by producing propionate and butyrate, which serve as HDAC inhibitors. This study provides a potential psychoprobiotic to reduce neuroinflammation.
Topics: Animals; Brain-Gut Axis; Butyrates; Clostridiales; Cytokines; Fatty Acids, Volatile; Germ-Free Life; Histone Deacetylase 1; Histones; Neuroinflammatory Diseases; Probiotics; Propionates; Rats
PubMed: 35819092
DOI: 10.1002/mnfr.202200164 -
Nutrients Jun 2023Low-grade inflammation and barrier disruption are increasingly acknowledged for their association with non-communicable diseases (NCDs). Short chain fatty acids (SCFAs),...
Butyrate Protects Barrier Integrity and Suppresses Immune Activation in a Caco-2/PBMC Co-Culture Model While HDAC Inhibition Mimics Butyrate in Restoring Cytokine-Induced Barrier Disruption.
Low-grade inflammation and barrier disruption are increasingly acknowledged for their association with non-communicable diseases (NCDs). Short chain fatty acids (SCFAs), especially butyrate, could be a potential treatment because of their combined anti-inflammatory and barrier- protective capacities, but more insight into their mechanism of action is needed. In the present study, non-activated, lipopolysaccharide-activated and αCD3/CD28-activated peripheral blood mononuclear cells (PBMCs) with and without intestinal epithelial cells (IEC) Caco-2 were used to study the effect of butyrate on barrier function, cytokine release and immune cell phenotype. A Caco-2 model was used to compare the capacities of butyrate, propionate and acetate and study their mechanism of action, while investigating the contribution of lipoxygenase (LOX), cyclooxygenase (COX) and histone deacetylase (HDAC) inhibition. Butyrate protected against inflammatory-induced barrier disruption while modulating inflammatory cytokine release by activated PBMCs (interleukin-1 beta↑, tumor necrosis factor alpha↓, interleukin-17a↓, interferon gamma↓, interleukin-10↓) and immune cell phenotype (regulatory T-cells↓, T helper 17 cells↓, T helper 1 cells↓) in the PBMC/Caco-2 co-culture model. Similar suppression of immune activation was shown in absence of IEC. Butyrate, propionate and acetate reduced inflammatory cytokine-induced IEC activation and, in particular, butyrate was capable of fully protecting against cytokine-induced epithelial permeability for a prolonged period. Different HDAC inhibitors could mimic this barrier-protective effect, showing HDAC might be involved in the mechanism of action of butyrate, whereas LOX and COX did not show involvement. These results show the importance of sufficient butyrate levels to maintain intestinal homeostasis.
Topics: Humans; Cytokines; Butyrates; Leukocytes, Mononuclear; Coculture Techniques; Histone Deacetylases; Caco-2 Cells; Propionates; Interleukins; Intestinal Mucosa
PubMed: 37375664
DOI: 10.3390/nu15122760 -
The Journal of Nutrition Jan 2023High amylose starchy foods modulate the postprandial metabolic response in humans. However, the mechanisms of their metabolic benefits and their impact on the subsequent... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
High amylose starchy foods modulate the postprandial metabolic response in humans. However, the mechanisms of their metabolic benefits and their impact on the subsequent meal have not been fully elucidated.
OBJECTIVE
We aimed to evaluate whether glucose and insulin responses to a standard lunch are influenced by the consumption of amylose-rich bread at breakfast in overweight adults and whether changes in plasma short chain fatty acids (SCFAs) concentrations contribute to their metabolic effects.
METHODS
Using a randomized crossover design, 11 men and 9 women, BMI 30 ± 3 kg/m, 48 ± 19 y, consumed at breakfast 2 breads made with high amylose flour (HAF): 85%-HAF (180 g) and 75%-HAF (170 g), and control bread (120 g) containing 100% conventional flour. Plasma samples were collected at fasting, 4 h after breakfast, and 2 h after a standard lunch to measure glucose, insulin, and SCFA concentrations. ANOVA posthoc analyses were used for comparisons.
RESULTS
Postprandial plasma glucose responses were 27% and 39% lower after breakfasts with 85%- and 70%-HAF breads than control bread (P = 0.026 and P = 0.003, respectively), with no difference after lunch. Insulin responses were not different between the 3 breakfasts, whereas there was a 28% lower response after the lunch following breakfast with 85%-HAF bread than the control (P = 0.049). Propionate concentrations increased from fasting by 9% and 12% 6 h after breakfasts with 85%- and 70%-HAF breads and decreased by 11% with control bread (P < 0.05). At 6 h after breakfast with 70%-HAF bread, plasma propionate and insulin were inversely correlated (r = -0.566; P = 0.044).
CONCLUSIONS
Amylose-rich bread reduces the postprandial glucose response after breakfast and insulin concentrations after the subsequent lunch in overweight adults. This second meal effect may be mediated by the elevation of plasma propionate due to intestinal fermentation of resistant starch. High amylose products could be a promising tool in a dietary prevention strategy for type 2 diabetes.
THIS TRIAL WAS REGISTERED AT CLINICAL TRIAL REGISTRY AS
NCT03899974 (https://www.
CLINICALTRIALS
gov/ct2/show/NCT03899974).
Topics: Adult; Female; Humans; Male; Amylose; Blood Glucose; Bread; Breakfast; Cross-Over Studies; Glucose; Insulin; Insulin, Regular, Human; Overweight; Postprandial Period; Propionates; Triticum
PubMed: 36913446
DOI: 10.1016/j.tjnut.2022.10.007