Short-chain fatty acids of various lengths differentially inhibit Klebsiella pneumoniae and Enterobacteriaceae species DOI Creative Commons
Kai Chirng Chang, Niranjan Nagarajan, Yunn‐Hwen Gan

et al.

mSphere, Journal Year: 2024, Volume and Issue: 9(2)

Published: Feb. 2, 2024

ABSTRACT The gut microbiota is inextricably linked to human health and disease. It can confer colonization resistance against invading pathogens either through niche occupation nutrient competition or via its secreted metabolites. Short-chain fatty acids (SCFA) are the primary metabolites in as a result of dietary fiber fermentation by microbiota. In this work, we demonstrate that interaction single-species commensals on solid media insufficient for pathogen inhibition, but supernatants from monocultures these commensal bacteria enriched acetate inhibition anaerobic growth enteric Klebsiella pneumoniae . three SCFAs (acetate, propionate, butyrate) strongly inhibit intestinal Escherichia coli Nissle well panel besides K. at physiological pH cecum ascending colon. This was significantly milder Bacteroides thetaiotaomicron Bifidobacterium adolescentis previously demonstrated be associated with recovery after antibiotic-induced dysbiosis. We describe general suppression bacterial membrane potential colonic pH. Furthermore, strength increases increasing alkyl chain length. Overall, insights gained study shed light therapeutic use conferring dysbiotic gut. IMPORTANCE Rising antimicrobial has made treatment infections increasingly difficult. According World Health Organization, it become burgeoning threat hospital public systems worldwide. largely attributed global rise carbapenem-resistant Enterobacteriaceae recent years, common hospital-acquired growing resistant last-line antibiotics. Antibiotics disrupt homeostatic balance microbiota, resulting loss pathogens. work describes ability short-chain (SCFAs) produced effective wide without major impact species. also undescribed link between length antibacterial effects SCFAs. SCFAs, thus, hold promise an alternative option leveraging activity endogenously disrupting homeostasis.

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

255
Faecalibacterium: a bacterial genus with promising human health applications DOI Creative Commons
Rebeca Martín, David Ríos-Covián, Eugénie Huillet

et al.

FEMS Microbiology Reviews, Journal Year: 2023, Volume and Issue: 47(4)

Published: July 1, 2023

Abstract In humans, many diseases are associated with alterations in gut microbiota, namely increases or decreases the abundance of specific bacterial groups. One example is genus Faecalibacterium. Numerous studies have underscored that low levels Faecalibacterium correlated inflammatory conditions, bowel disease (IBD) forefront. Its representation also diminished case several diseases, including colorectal cancer (CRC), dermatitis, and depression. Additionally, relative presence this considered to reflect, at least part, intestinal health status because frequently present reduced individuals gastrointestinal disorders. review, we first thoroughly describe updates taxonomy Faecalibacterium, which has transformed a single-species taxon multispecies over last decade. We then explore links discovered between various since IBD-focused were published. Next, examine current available strategies for modulating gut. Finally, summarize mechanisms underlying beneficial effects been attributed genus. Together, epidemiological experimental data strongly support use as next-generation probiotic (NGP) live biotherapeutic product (LBP).

Language: Английский

Citations

192
Microbiome diversity protects against pathogens by nutrient blocking DOI
Frances Spragge, Erik Bakkeren, Martin T. Jahn

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6676)

Published: Dec. 14, 2023

The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack ability to predict which communities will be protective. We studied how bacteria influence two major bacterial both vitro and gnotobiotic mice. Whereas single species alone had negligible effects, resistance greatly increased with community diversity. Moreover, this community-level rested critically upon certain being present. explained these ecological patterns through collective resistant consume nutrients that overlap those used pathogen. Furthermore, applied our findings successfully resist a novel target strain. Our work provides reason why diversity is beneficial suggests route for rational design pathogen-resistant communities.

Language: Английский

Citations

166
Drug-microbiota interactions: an emerging priority for precision medicine DOI Creative Commons
Qing Zhao, Yao Chen, Weihua Huang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 9, 2023

Abstract Individual variability in drug response (IVDR) can be a major cause of adverse reactions (ADRs) and prolonged therapy, resulting substantial health economic burden. Despite extensive research pharmacogenomics regarding the impact individual genetic background on pharmacokinetics (PK) pharmacodynamics (PD), diversity explains only limited proportion IVDR. The role gut microbiota, also known as second genome, its metabolites modulating therapeutic outcomes human diseases have been highlighted by recent studies. Consequently, burgeoning field pharmacomicrobiomics aims to explore correlation between microbiota variation IVDR or ADRs. This review presents an up-to-date overview intricate interactions classical agents for systemic diseases, including cancer, cardiovascular (CVDs), endocrine others. We summarise how directly indirectly, modify absorption, distribution, metabolism, excretion (ADME) drugs. Conversely, drugs modulate composition function leading changes microbial metabolism immune response. discuss practical challenges, strategies, opportunities this field, emphasizing critical need develop innovative approach multi-omics, integrate various data types, genomic data, well translate lab into clinical practice. To sum up, represents promising avenue address improve patient outcomes, further is imperative unlock full potential precision medicine.

Language: Английский

Citations

88
Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease? DOI Creative Commons
Lei Li,

Peilan Peng,

Ning Ding

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 967 - 967

Published: April 20, 2023

Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted associated with oxidative stress, unbalanced gut microbiota, aberrant immune response. Indeed, stress can affect the progression development by regulating homeostasis microbiota Therefore, redox-targeted therapy promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, able to maintain redox equilibrium in tract prevent abnormal radical responses. Here, we provide comprehensive perspective implementing antioxidants as potential candidate medications. In addition, demonstrate novel technologies stratagems promoting antioxidative properties CHM-derived including delivery systems, chemical modifications, combination strategies.

Language: Английский

Citations

65
Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD) DOI Creative Commons
Raquel Benedé‐Ubieto, Francisco Javier Cubero, Yulia A. Nevzorova

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: March 21, 2024

Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty (NAFLD), a growing health concern. The complex progression of MASLD extends beyond liver, driven by "gut-liver axis," where diet, genetics, gut-liver interactions influence disease development. pathophysiology involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, fibrosis, with subsequent risk hepatocellular carcinoma (HCC). gut, tripartite barrier, mechanical, immune, microbial components, engages constant communication liver. Recent evidence links dysbiosis disrupted barriers to systemic inflammation progression. Toll-like receptors (TLRs) mediate immunological crosstalk between recognizing structures triggering immune responses. "multiple hit model" development factors like resistance, dysbiosis, genetics/environmental elements disrupting axis, leading impaired intestinal barrier function increased permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, modulation approaches through prebiotics, probiotics, symbiotics, fecal microbiota transplantation (FMT). This review underscores microbiome, their impact on therapeutic prospects.

Language: Английский

Citations

59
Antibiotic-induced collateral damage to the microbiota and associated infections DOI
Laura de Nies, Carolin M. Kobras, Mathew Stracy

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(12), P. 789 - 804

Published: Aug. 4, 2023

Language: Английский

Citations

52
Microbial transmission in the social microbiome and host health and disease DOI Creative Commons
Amar Sarkar,

Cameron J.A. McInroy,

Siobhán Harty

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(1), P. 17 - 43

Published: Jan. 1, 2024

Language: Английский

Citations

38
The conceptual foundations of innate immunity: Taking stock 30 years later DOI Creative Commons
Thomas Pradeu, Bart P. H. J. Thomma, Stephen E. Girardin

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 613 - 631

Published: April 1, 2024

SummaryWhile largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding immunology. Innate provides first barrier infection in vertebrates, and it is sole mechanism host defense invertebrates plants. also plays a critical role maintaining homeostasis, shaping microbiota, disease contexts such as cancer, neurodegeneration, metabolic syndromes, aging. The emergence field has led an expanded view system, no longer restricted vertebrates instead concerns all metazoans, plants, even prokaryotes. study given rise new concepts language. Here, we review history definition core immunity, discussing their value fruitfulness long run.

Language: Английский

Citations

36
Commensal lifestyle regulated by a negative feedback loop between Arabidopsis ROS and the bacterial T2SS DOI Creative Commons
Frederickson Entila, Xiaowei Han, Akira Mine

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 11, 2024

Despite the plant health-promoting effects of microbiota, these assemblages also comprise potentially detrimental microbes. How immunity controls its microbiota to promote health under conditions remains largely unknown. We find that commensal bacteria isolated from healthy Arabidopsis plants trigger diverse patterns reactive oxygen species (ROS) production dependent on immune receptors and completely NADPH oxidase RBOHD selectively inhibited specific commensals, notably Xanthomonas L148. Through random mutagenesis, we L148 gspE, encoding a type II secretion system (T2SS) component, is required for damaging rbohD mutant plants. In planta bacterial transcriptomics reveals suppresses most T2SS gene expression including gspE. colonization protected against pathogen, when gspE was by ROS or mutation. Thus, negative feedback loop between tames leaf turns it into microbe beneficial host.

Language: Английский

Citations

32