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Microbiome Sep 2023Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3....
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3. The clinical manifestations are influenced by genetic and environmental factors that may include gut microbiome.
RESULTS
We investigated the fecal metagenome, fecal metabolome, serum metabolome, neurotransmitters, and cytokines in a cohort of 24 CADASIL patients with 28 healthy household controls. The integrated-omics study showed CADASIL patients harbored an altered microbiota composition and functions. The abundance of bacterial coenzyme A, thiamin, and flavin-synthesizing pathways was depleted in patients. Neurotransmitter balance, represented by the glutamate/GABA (4-aminobutanoate) ratio, was disrupted in patients, which was consistent with the increased abundance of two major GABA-consuming bacteria, Megasphaera elsdenii and Eubacterium siraeum. Essential inflammatory cytokines were significantly elevated in patients, accompanied by an increased abundance of bacterial virulence gene homologs. The abundance of patient-enriched Fusobacterium varium positively correlated with the levels of IL-1β and IL-6. Random forest classification based on gut microbial species, serum cytokines, and neurotransmitters showed high predictivity for CADASIL with AUC = 0.89. Targeted culturomics and mechanisms study further showed that patient-derived F. varium infection caused systemic inflammation and behavior disorder in Notch3 mice potentially via induction of caspase-8-dependent noncanonical inflammasome activation in macrophages.
CONCLUSION
These findings suggested the potential linkage among the brain-gut-microbe axis in CADASIL. Video Abstract.
Topics: Animals; Mice; CADASIL; Gastrointestinal Microbiome; Mental Disorders; Cytokines; gamma-Aminobutyric Acid
PubMed: 37684694
DOI: 10.1186/s40168-023-01638-3 -
Applied and Environmental Microbiology Dec 2012The growth of Megasphaera elsdenii on lactate with acrylate and acrylate analogues was studied under batch and steady-state conditions. Under batch conditions, lactate...
The growth of Megasphaera elsdenii on lactate with acrylate and acrylate analogues was studied under batch and steady-state conditions. Under batch conditions, lactate was converted to acetate and propionate, and acrylate was converted into propionate. Acrylate analogues 2-methyl propenoate and 3-butenoate containing a terminal double bond were similarly converted into their respective saturated acids (isobutyrate and butyrate), while crotonate and lactate analogues 3-hydroxybutyrate and (R)-2-hydroxybutyrate were not metabolized. Under carbon-limited steady-state conditions, lactate was converted to acetate and butyrate with no propionate formed. As the acrylate concentration in the feed was increased, butyrate and hydrogen formation decreased and propionate was increasingly generated, while the calculated ATP yield was unchanged. M. elsdenii metabolism differs substantially under batch and steady-state conditions. The results support the conclusion that propionate is not formed during lactate-limited steady-state growth because of the absence of this substrate to drive the formation of lactyl coenzyme A (CoA) via propionyl-CoA transferase. Acrylate and acrylate analogues are reduced under both batch and steady-state growth conditions after first being converted to thioesters via propionyl-CoA transferase. Our findings demonstrate the central role that CoA transferase activity plays in the utilization of acids by M. elsdenii and allows us to propose a modified acrylate pathway for M. elsdenii.
Topics: Acetates; Acrylates; Adenosine Triphosphate; Carbon; Energy Metabolism; Lactic Acid; Megasphaera; Propionates
PubMed: 23023753
DOI: 10.1128/AEM.02443-12 -
Scientific Reports May 2022This study aimed to evaluate the effects of Saccharomyces cerevisiae and Megasphaera elsdenii as direct fed microbials (DFM) in beef cattle finishing diets to alleviate...
This study aimed to evaluate the effects of Saccharomyces cerevisiae and Megasphaera elsdenii as direct fed microbials (DFM) in beef cattle finishing diets to alleviate acute ruminal lactic acidosis in vitro. A dual-flow continuous culture system was used. Treatments were a Control, no DFM; YM1, S. cerevisiae and M. elsdenii strain 1; YM2, S. cerevisiae and M. elsdenii strain 2; and YMM, S. cerevisiae and half of the doses of M. elsdenii strain 1 and strain 2. Each DFM dose had a concentration of 1 × 10 CFU/mL. Four experimental periods lasted 11 days each. For the non-acidotic days (day 1-8), diet contained 50:50 forage to concentrate ratio. For the challenge days (day 9-11), diet contained 10:90 forage to concentrate ratio. Acute ruminal acidosis was successfully established. No differences in pH, D-, L-, or total lactate were observed among treatments. Propionic acid increased in treatments containing DFM. For N metabolism, the YMM treatment decreased protein degradation and microbial protein synthesis. No treatment effects were observed on NH-N concentration; however, efficiency of N utilization by ruminal bacteria was greater than 80% during the challenge period and NH-N concentration was reduced to approximately 2 mg/dL as the challenge progressed.
Topics: Acidosis; Animal Feed; Animals; Cattle; Diet; Fermentation; Hydrogen-Ion Concentration; Megasphaera elsdenii; Rumen; Saccharomyces cerevisiae
PubMed: 35562415
DOI: 10.1038/s41598-022-11959-2 -
Journal of Reproductive Immunology Apr 2020Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria leads to bacterial vaginosis (BV) which is associated with increased inflammation in...
Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria leads to bacterial vaginosis (BV) which is associated with increased inflammation in the genital mucosa. Moreover, BV increases susceptibility to sexual transmitted infections (STIs) and is associated with adverse pregnancy outcomes. It remains unclear how specific vaginal aerobic and anaerobic bacteria affect health and disease. We selected different vaginal bacteria ranging from true commensals to species associated with dysbiosis and investigated their effects on activation of dendritic cells (DCs). Commensal Lactobacilli crispatus did not induce DC maturation nor led to production of pro-inflammatory cytokines. In contrast, BV-associated bacteria Megasphaera elsdenii and Prevotella timonensis induced DC maturation and increased levels of pro-inflammatory cytokines. Notably, DCs stimulated with Prevotella timonensis suppressed Th2 responses and induced Th1 skewing, typically associated with preterm birth. In contrast, Lactobacillus crispatus and Megasphaera elsdenii did not affect Th cell polarization. These results strongly indicate that the interaction of vaginal bacteria with mucosal DCs determines mucosal inflammation and we have identified the anaerobic bacterium Prevotella timonensis as a strong inducer of inflammatory responses. Specifically targeting these inflammation-inducing bacteria might be a therapeutic strategy to prevent BV and associated risks in STI susceptibility and preterm birth.
Topics: Cells, Cultured; Cytokines; Dendritic Cells; Dysbiosis; Female; Humans; Inflammation Mediators; Leukocytes, Mononuclear; Megasphaera elsdenii; Prevotella; Primary Cell Culture; Vagina; Vaginosis, Bacterial
PubMed: 32004804
DOI: 10.1016/j.jri.2020.103085 -
Translational Animal Science 2023Our objective was to evaluate the effects of combinations of and as direct-fed microbials (DFM) on ruminal microbiome during an acute acidosis challenge in a...
Our objective was to evaluate the effects of combinations of and as direct-fed microbials (DFM) on ruminal microbiome during an acute acidosis challenge in a continuous culture system. Treatments provided a DFM dose of 1 × 10 colony-forming unit (CFU)/mL, as follows: control (no DFM), YM1 ( and strain 1), YM2 ( and strain 2), and YMM ( and half of the doses of strains 1 and 2). We conducted four experimental periods of 11 d, which consisted of non-acidotic days (1 to 8) and acidotic challenge days (9 to 11) to establish acute ruminal acidosis conditions with a common basal diet containing 12% neutral detergent fiber and 58% starch. Treatments were applied from days 8 to 11, and samples of liquid and solid-associated bacteria were collected on days 9 to 11. Overall, 128 samples were analyzed by amplification of the V4 region of bacterial 16S rRNA, and data were analyzed with R and SAS for alpha and beta diversity, taxa relative abundance, and correlation of taxa abundance with propionate molar proportion. We observed a lower bacterial diversity (Shannon index, = 0.02) when YM1 was added to the diet in comparison to the three other treatments. Moreover, compared to control, addition of YM1 to the diet increased relative abundance of phylum ( = 0.05) and family ( = 0.05) in the solid fraction and tended to increase abundance of family ( = 0.10) and genus ( = 0.09) in the liquid fraction. Correlation analysis indicated a positive association between propionate molar proportion and relative abundance of ( = 0.36, = 0.04) and ( = 0.36, = 0.05) in the solid fraction. The inclusion of YM1 in high-grain diets with a high starch content resulted in greater abundance of bacteria involved in succinate synthesis which may have provided the substrate for the greater propionate synthesis observed.
PubMed: 38023425
DOI: 10.1093/tas/txad123 -
Translational Animal Science Jul 2021This study evaluated the effects of administration at the beginning of the feedlot period on performance of bulls. On d 0, 383 Nellore bulls (initial shrunk body...
This study evaluated the effects of administration at the beginning of the feedlot period on performance of bulls. On d 0, 383 Nellore bulls (initial shrunk body weight 384 ± 29.2 kg; initial age = 24 ± 2 mo) were assigned to treatments in a randomized complete block design. Treatments consisted of 1) 14 d adaptation diet and transition to a finishing diet (), 2) CONT plus oral administration of 20 mL of Lactipro-NXT () on d 0 of the study (), 3) CONT diet, consisting of 6 d of adaptation diet plus oral administration of 20 mL of Lactipro-NXT on d 0 of the study (), and 4) No adaptation diet and oral administration of 20 mL of Lactipro-NXT on d 0 of the study (). Experimental period lasted 119 d. No treatment effects were observed for any of the performance parameters evaluated herein ( ≥ 0.15). Nonetheless, a treatment × wk interaction was observed for DM, NE, and NE intakes ( < 0.0001). For all these parameters, MEG-0 and MEG-6 had a reduced intake vs. MEG-14 and CONT in the first wk of the study ( ≤ 0.05). For the carcass traits, no effects were observed for HCW ( ≥ 0.24), whereas MEG-6 had a greater REA when compared with MEG-0 and MEG-14 (quadratic effect; = 0.04) and MEG-administered bulls tended to have a greater BFT vs. CONT ( = 0.08). In summary, administration at the beginning of the feedlot period did not improve performance, whereas reducing the length of the adaptation period for 6 d improved REA of finishing bulls.
PubMed: 34790892
DOI: 10.1093/tas/txab091 -
Animal Bioscience Jun 2023This study was conducted to evaluate the use of Megasphaera elsdenii (M. elsdenii) as a probiotic on rumen fermentation, production performance, carcass traits and...
OBJECTIVE
This study was conducted to evaluate the use of Megasphaera elsdenii (M. elsdenii) as a probiotic on rumen fermentation, production performance, carcass traits and health of ruminants by integrating data from various related studies using meta-analysis.
METHODS
A total of 32 studies (consisted of 136 data points) were obtained and integrated into a database. The parameters integrated were fermentation products, rumen microbes, production performance, carcass quality, animal health, blood and urine metabolites. Statistical analysis of the compiled database used a mixed model methodology. Different studies were considered random effects, while M. elsdenii supplementation doses were considered fixed effects. p-values and the Akaike information criterion were employed as model statistics. The model was deemed significant at p<0.05 or had a tendency to be significant when p-value between 0.05〈p〈0.10.
RESULTS
Supplementation with M. elsdenii increased (p<0.05) some proportion of fermented rumen products such as propionate, butyrate, isobutyrate, and valerate, and significantly reduced (p<0.05) lactic acid concentration, acetate proportion, total bacterial population and methane emission. Furthermore, the probiotic supplementation enhanced (p<0.05) livestock production performance, especially in the average daily gain and body condition score. Regarding the carcass quality, hot carcass weight and carcass gain were elevated (p<0.05) due to the M. elsdenii supplementation. Animal health also showed improvement as indicated by the lower (p<0.05) diarrhoea and bloat incidences as well as the liver abscess. However, M. elsdenii supplementation had negligible effects on blood and urine metabolites of ruminants.
CONCLUSION
Supplementation of M. elsdenii is capable of decreasing ruminal lactic acid concentration, enhancing rumen health, elevating some favourable rumen fermentation products, and in turn, increasing production performance of ruminants.
PubMed: 36634661
DOI: 10.5713/ab.22.0258 -
Animal Nutrition (Zhongguo Xu Mu Shou... Jun 2022Shaziling pig, a Chinese indigenous breed, has been classified as a fatty pig model. However, the gut microbial development and role in lipid metabolism in Shaziling...
Shaziling pig, a Chinese indigenous breed, has been classified as a fatty pig model. However, the gut microbial development and role in lipid metabolism in Shaziling pigs has been rarely reported. Here, we compared the lipid metabolic and microbial profiles at 30, 60, 90, 150, 210, and 300 d of age between Shaziling and Yorkshire pigs. Predictably, there were marked differences in the liver lipids (i.e., cholesterol, glucose, and low-density lipoprotein) and the lipid related expressions (i.e., , /, /, and -) between Shaziling and Yorkshire pigs. Bacteria sequencing in the ileal digesta and mucosa showed that Shaziling pigs had a higher α-diversity and higher abundances of probiotics, such as , , and . Thirty-five differentiated metabolites were further identified in the mucosa between Shaziling and Yorkshire pigs, which were enriched in the carbohydrate, protein, glucose and amino acid metabolism and bile acid biosynthesis. Furthermore, 7 differentiated microbial species were markedly correlated with metabolites, indicating the role of gut microbiota in the host metabolism. Next, the role of differentiated in lipid metabolism was validated in Duroc × Landrace × Yorkshire (DLY) pigs and the results showed that mono-colonization promoted lipid deposition and metabolism by altering gut microbiota (i.e., and ) and // gene expressions. In conclusion, Shaziling pigs exhibited different metabolic and microbial profiles compared with Yorkshire pigs, which might have contributed to the diverse metabolic phenotypes, and the significant enrichment of in Shaziling pigs promoted lipid metabolism and obesity of DLY pigs, which provided a novel idea to improve the fat content of lean pigs.
PubMed: 35600540
DOI: 10.1016/j.aninu.2021.10.012 -
Translational Animal Science Apr 2020Simmental-Angus calves [ = 135; 72 steers and 63 heifers; body weight (BW) = 212.4 kg ± 36.1] were early weaned (~5 mo) to evaluate multiple feeding regimens...
Simmental-Angus calves [ = 135; 72 steers and 63 heifers; body weight (BW) = 212.4 kg ± 36.1] were early weaned (~5 mo) to evaluate multiple feeding regimens (conventional vs. aggressive energy diets ± NCIMB 41125 ( culture (MEC); Lactipro Advance; MS Biotec Inc., Wamego, KS) in order to elucidate the optimal development strategy. Objectives were measured by tracking the effects of caloric density and oral drenching of growing phase performance and subsequent carcass traits. The 72-d experiment featured three groups: 1) control (CON), fed exclusively a 35% roughage diet; 2) aggressive (AGR), fed a blend of a 10% and 35% roughage diets; 3) MEC, fed the same diet as AGR and drenched with 50 mL of NCIMB 41125 on day 1. A subset of calves ( = 45) was equipped with wireless rumination tags (Allflex Flex Tag; SCR Engineers, Ltd; Netanya, Israel), which logged daily rumination and general activity. Skeletal growth variables were assessed by measuring wither and hip height pretrial and posttrial. Ultrasonography provided additional resolution concerning growing phase compositional gain, which was later verified by carcass data collection. Data were analyzed as a nested analysis of variance with BW and gender serving as blocking factors. The increased caloric density of the diets administered to MEC and AGR calves resulted in greater average daily gain and gain:feed values compared with CON even during the first 21 d of diet acclimation ( ≤ 0.05). Additional fiber concentration of CON diets led to increased rumination times in 9 of the 10 wk of trial ( ≤ 0.10). No differences amongst treatments were detected for skeletal variables or ultrasound 12th rib fat. Cattle fed CON diets posted 3.4% inferior BW at the end of the growing period trial and a 3.8% reduction in hot carcass weight (HCW), reinforcing the theory that intensifying caloric intake during the growing phase does not compromise future feedlot performance. Ultrasound marbling scores for MEC-treated cattle were 19° greater than AGR treated cattle ( ≤ 0.05) at the end of the growing phase trial. Nearly the exact same advantage (22°) was observed in the cooler 5 mo later ( = 0.42). Implying MEC metabolically imprinted cattle to favor marbling development. It appears that maximizing dietary caloric density in light-weight calves does not adversely affect the growth curve, while oral dosing of MEC during the growing period may be a precursor for enhanced quality grade.
PubMed: 32705029
DOI: 10.1093/tas/txaa031 -
Frontiers in Microbiology 2019is an ecologically important rumen bacterium that metabolizes lactate and relieves rumen acidosis (RA) induced by a high-grain-diet. Understanding the regulatory...
is an ecologically important rumen bacterium that metabolizes lactate and relieves rumen acidosis (RA) induced by a high-grain-diet. Understanding the regulatory mechanisms of the lactate metabolism of this species in RA conditions might contribute to developing dietary strategies to alleviate RA. was co-cultured with four lactate producers (, , , and ) and a series of substrate starch doses (1, 3, and 9 g/L) were used to induce one normal and two RA models (subacute rumen acidosis, SARA and acute rumen acidosis, ARA) under batch conditions. The associations between bacterial competition and the shift of organic acids' (OA) accumulation patterns in both statics and dynamics manners were investigated in RA models. Furthermore, we examined the effects of substrate lactate concentration and pH on lactate degradation pattern and genes related to the lactate utilizing pathways in the continuous culture. The positive growth of and caused OA accumulation in the SARA model to shift from lactate to butyrate and resulted in pH recovery. Furthermore, both the quantities of substrate lactate and pH had remarkable effects on lactate utilization due to the transcriptional regulation of metabolic genes, and the lactate utilization in was more sensitive to pH changes than to the substrate lactate level. In addition, compared with associations based on statics data, associations discovered from dynamics data showed greater significance and gave additional explanations regarding the relationships between bacterial competition and OA accumulation.
PubMed: 30792704
DOI: 10.3389/fmicb.2019.00162