N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory lo...N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.展开更多
Background Our previous study demonstrated that dietary supplementation of Bacillus subtilis enhanced growth performance and intestinal integrity in weaned pigs challenged with enterotoxigenic Escherichia coli(ETEC).T...Background Our previous study demonstrated that dietary supplementation of Bacillus subtilis enhanced growth performance and intestinal integrity in weaned pigs challenged with enterotoxigenic Escherichia coli(ETEC).Therefore,this study aimed to explore the impact of Bacillus subtilis on gut health and its role in modulating host–microbe interactions in post-weaning pigs.Results ETEC infection disrupted key metabolic pathways in distal colon,including glutathione,beta-alanine,and pyrimidine metabolism,indicating increased oxidative stress,impaired nucleotide balance,and amino acid catabolic stress.Bacillus subtilis supplementation induced distinct metabolomic and microbiome profiles in colon digesta of weaned pigs challenged with ETEC.Bacillus subtilis-treated pigs under ETEC challenge exhibited significant enrichment in amino acid-and energy-related pathways such as arginine biosynthesis,phenylalanine metabolism,pantothenate and CoA biosynthesis.ETEC infection induced microbial dysbiosis in the distal colon,resulting in decrease(P<0.05)in abundance of Streptococcaceae and Enterobacteriaceae compared to healthy controls.Bacillus subtilis supplementation mitigated the ETEC-induced disruptions by increasing the relative abundance of beneficial bacterial families,including Lachnospiraceae and Bacteroidaceae.Conclusion Supplementation of Bacillus subtilis improves intestinal health and resilience against ETEC challenge by mitigating infection-induced metabolic disruptions and gut dysbiosis in weaned pigs.展开更多
It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mo...It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.展开更多
基金supported by the National Institute on Aging(Nos.AG000723 and AG000578)(to VAB)the Fondation Sante(No.19656),Greece 2.0+1 种基金the National Recovery and Resilience Plan’s flagship program TAEDR-0535850the European Research Council(No.101077374-Synapto Mitophagy)(to KP)。
文摘N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.
基金supported by the United States Department of Agriculture(USDA)National Institute of Food and Agriculture,multistate project W4002。
文摘Background Our previous study demonstrated that dietary supplementation of Bacillus subtilis enhanced growth performance and intestinal integrity in weaned pigs challenged with enterotoxigenic Escherichia coli(ETEC).Therefore,this study aimed to explore the impact of Bacillus subtilis on gut health and its role in modulating host–microbe interactions in post-weaning pigs.Results ETEC infection disrupted key metabolic pathways in distal colon,including glutathione,beta-alanine,and pyrimidine metabolism,indicating increased oxidative stress,impaired nucleotide balance,and amino acid catabolic stress.Bacillus subtilis supplementation induced distinct metabolomic and microbiome profiles in colon digesta of weaned pigs challenged with ETEC.Bacillus subtilis-treated pigs under ETEC challenge exhibited significant enrichment in amino acid-and energy-related pathways such as arginine biosynthesis,phenylalanine metabolism,pantothenate and CoA biosynthesis.ETEC infection induced microbial dysbiosis in the distal colon,resulting in decrease(P<0.05)in abundance of Streptococcaceae and Enterobacteriaceae compared to healthy controls.Bacillus subtilis supplementation mitigated the ETEC-induced disruptions by increasing the relative abundance of beneficial bacterial families,including Lachnospiraceae and Bacteroidaceae.Conclusion Supplementation of Bacillus subtilis improves intestinal health and resilience against ETEC challenge by mitigating infection-induced metabolic disruptions and gut dysbiosis in weaned pigs.
基金Israel Cancer Research FoundationSamuel Waxman Cancer Research FoundationCore funding from Tel Aviv University。
文摘It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.
