Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function DOI Creative Commons
Johannes P. Johnson-Martínez, Christian Diener,

Anne E. Levine

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(7), P. 101646 - 101646

Published: July 1, 2024

Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation associated with an ecosystem-wide switch from fiber fermentation short-chain fatty acid production more detrimental protein toxin production. Here, we analyze multi-omic data generally healthy adults see how BMF affects their molecular phenotypes, in a pre-disease context. Results show differential abundances of microbial genera, blood metabolites, variation lifestyle factors across categories. These differences relate inflammation, heart health, liver function, function. Causal mediation analysis indicates association between lower reduced function partially mediated by microbially derived 3-indoxyl sulfate (3-IS). This result, context, suggests accumulation microbiota-derived toxins abnormal precede organ damage may be drivers chronic, aging-related diseases.

Language: Английский

The Influence of Gut Microbiota on Oxidative Stress and the Immune System DOI Creative Commons

C Kunst,

Stephan Schmid,

M Michalski

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1388 - 1388

Published: May 8, 2023

The human gastrointestinal tract is home to a complex microbial community that plays an important role in the general well-being of entire organism. gut microbiota generates variety metabolites and thereby regulates many biological processes, such as regulation immune system. In gut, bacteria are direct contact with host. major challenge here prevent unwanted inflammatory reactions on one hand other ensure system can be activated when pathogens invade. Here REDOX equilibrium utmost importance. This controlled by either directly or indirectly via bacterial-derived metabolites. A balanced microbiome sorts for stable balance, whereas dysbiosis destabilizes this equilibrium. An imbalanced status affects disrupting intracellular signaling promoting responses. we (i) focus most common reactive oxygen species (ROS) (ii) define transition from state oxidative stress. Further, (iii) describe ROS regulating Thereafter, (iv) examine influence homeostasis how shifts pro- anti-oxidative cellular conditions suppress promote responses inflammation.

Language: Английский

Citations

78
Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis DOI Creative Commons
Zihong Wu, Yuqing Huang, Renyi Zhang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 7, 2024

Abstract Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher than women. Research suggests that this difference may be attributed to variations sex steroid hormone levels gut microbiome. The microbiome CRC shows composition function between sexes, leading concept ‘microgenderome’ ‘sex hormone–gut axis.’ Conventional research indicates estrogens, by promoting more favorable microbiota, reduce risk CRC. Conversely, androgens have direct pro-tumorigenic effect increasing proportion opportunistic pathogens. microbiota also influence expressing specific enzymes or directly affecting gonadal function. However, area remains controversial. This review aims explore differences incidence, phenomenon sexual within microbiome, intricate interplay axis objective is gain better understanding these interactions their potential clinical implications, as well introduce innovative approaches treatment. Graphical

Language: Английский

Citations

19
Microbiome-Driven Therapeutics: From Gut Health to Precision Medicine DOI Creative Commons
Muneer Yaqub,

Aashika Jain,

Chinedu Eucharia Joseph

et al.

Gastrointestinal Disorders, Journal Year: 2025, Volume and Issue: 7(1), P. 7 - 7

Published: Jan. 15, 2025

The human microbiome, a complex ecosystem of microorganisms residing in and on the body, plays pivotal role regulation wide range physiological processes, including digestion, immune responses, metabolic functions. In recent years, rapidly growing field microbiome-driven therapeutics has garnered significant attention owing to its potential revolutionize healthcare. This review explores evolving landscape microbiome-based therapies, with particular focus gut microbiome implications for both health precision medicine. We highlight advances understanding how microbial communities influence disease pathogenesis treatment outcomes, spanning conditions such as inflammatory bowel (IBD), disorders, neurological diseases, even cancer. article also discusses emerging therapeutic strategies, probiotics, prebiotics, fecal microbiota transplantation (FMT), microbial-based drugs, well challenges associated their clinical implementation. Additionally, we examined integration profiling metagenomic data is advancing medicine, paving way personalized effective treatments. serves comprehensive resource that synthesizes current knowledge, identifies key gaps research, offers insights into future direction therapeutics, thus providing valuable framework clinicians, researchers, policymakers seeking harness microbiomes advance healthcare solutions.

Language: Английский

Citations

2
The tumor microenvironment and dendritic cells: Developers of pioneering strategies in colorectal cancer immunotherapy? DOI
Farid Ghorbaninezhad, Mina Afrashteh Nour,

Omid Rahbar Farzam

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(2), P. 189281 - 189281

Published: Feb. 8, 2025

Language: Английский

Citations

2
Gut microbiota modulation: a tool for the management of colorectal cancer DOI Creative Commons
Yan Wang, Hui Li

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: April 21, 2022

Abstract Colorectal cancer (CRC) is the second cause of death and third most frequently diagnosed cancer. Besides lifestyle, genetic epigenetic alterations, environmental factors, gut microbiota also plays a vital role in CRC development. The interruption commensal relationship between host could lead to an imbalance bacteria population, which pathogenic become predominant population gut. Different therapeutic strategies have been developed modify immune system, prevent pathogen colonization, alter activity composition microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, fecal transplantation (FMT). Even though employed exhibit promising results, their translation into clinic requires evaluating potential implications risks, well assessment long-term effects. This study was set review imbalances with effects on therapy, including chemotherapy immunotherapy. More importantly, we reviewed that used modulate impact treatment CRC, challenges each strategy.

Language: Английский

Citations

41
Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond DOI Creative Commons
Samar Al Bitar,

Marwan El‐Sabban,

Samer Doughan

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(9), P. 1395 - 1426

Published: March 7, 2023

Colorectal cancer (CRC) is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide. Despite advances in therapeutic regimens, number patients presenting with metastatic CRC (mCRC) increasing due to resistance therapy, conferred by small population cells, known as stem cells. Targeted therapies have been highly successful prolonging overall survival mCRC. Agents are being developed target key molecules involved drug-resistance metastasis CRC, these include vascular endothelial growth factor, epidermal factor receptor, human receptor-2, mitogen-activated extracellular signal-regulated kinase, addition immune checkpoints. Currently, there several ongoing clinical trials newly targeted agents, which shown considerable efficacy improved prognosis who do not benefit from conventional chemotherapy. In this review, we highlight recent developments use existing novel agents against drug-resistant Furthermore, discuss limitations challenges associated therapy strategies combat intrinsic acquired therapies, importance implementing better preclinical models application personalized based on predictive biomarkers for treatment selection.

Language: Английский

Citations

37
Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach DOI Creative Commons
Somrita Padma, Ritwik Patra, Parth Sarthi Sen Gupta

et al.

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 525 - 525

Published: Feb. 23, 2023

Colorectal cancer (CRC) is one of the most common cancers and second-highest in cancer-related deaths worldwide. The changes gut homeostasis microbial dysbiosis lead to initiation tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are principal contributors induction pathogenesis CRC. Thus, inhibiting growth survival these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) an essential membrane protein F. that promotes adherence bacterium colon cells, recruitment immune tumorigenesis. present study depicts design silico vaccine candidate comprising B-cell T-cell epitopes Fap2 for improving cell-mediated humoral responses against Notably, this participates significant protein-protein interactions with human Toll-like receptors, especially TLR6 reveals, which likely correlated its efficacy eliciting potential responses. immunogenic trait designed was verified by simulation approach. cDNA construct cloned within expression vector pET30ax expression. Collectively, proposed may serve as promising therapeutic intervening nucleatum-induced

Language: Английский

Citations

27
Human microbiomes in cancer development and therapy DOI Creative Commons
Chenglai Xia, Jiyan Su, Can Liu

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(2)

Published: Feb. 26, 2023

Colonies formed by bacteria, archaea, fungi, and viral groups their genomes, metabolites, expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis disease progression were link to Different organ sources, microbial species, metabolites are different; the mechanisms of carcinogenic or procancerous also different. Here, we summarize how microbiomes contribute in cancers skin, mouth, esophagus, lung, gastrointestinal, genital, blood, lymph malignancy. We insight into molecular triggering, promoting, inhibiting progress induced or/and secretions bioactive metabolites. And then, strategies application microorganisms cancer treatment discussed detail. However, which function still poorly understood. The bidirectional interactions between microbiotas endocrine systems need be clarified. Probiotics prebiotics believed benefit health via a variety mechanisms, particular, tumor inhibition. It is largely unknown agents cause progresses. expect this review may open new perspectives on possible therapeutic approaches patients with cancer.

Language: Английский

Citations

27
Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice DOI Creative Commons
Xing Kang,

Siu-Kin Ng,

Changan Liu

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 93, P. 104670 - 104670

Published: June 19, 2023

Obesity is a risk factor for colorectal cancer (CRC). The role of gut microbiota in mediating the cancer-promoting effect obesity unknown.Azoxymethane (AOM)-treated, ApcMin/+ and germ-free mice were gavaged with feces from obese individuals control subjects respectively. colonic tumor load number recorded at endpoint two carcinogenic models. composition transcriptome assessed by metagenomic sequencing RNA sequencing, anticancer effects bacteria depleted fecal samples validated.Conventional AOM-treated receiving showed significantly increased colon formation compared those subjects. impaired intestinal barrier function significant upregulation pro-inflammatory cytokines activation oncogenic Wnt signaling pathway. Consistently, transferring to led cell proliferation, impairment, induction proinflammatory gene expression. Moreover, transplanted human donors had abundance potential pathobiont Alistipes finegoldii, reduced commensals Bacteroides vulgatus Akkermansia muciniphila normal body mass index (BMI). Validation experiments that B. A. demonstrated anti-proliferative CRC, while finegoldii promoted CRC growth.Our results supported obesity-associated carcinogenesis identified putative bacterial candidates may mediate its mechanisms. Microbiota modulation provide new approaches prevent or treat obesity-related cancers including CRC.This work was funded National Key Research Development Program China (2020YFA0509200/2020YFA0509203), Natural Science Foundation (81922082), RGC Theme-based Scheme Hong Kong (T21-705/20-N), Impact Fund (R4632-21F), RGC-CRF (C4039-19GF C7065-18GF), RGC-GRF (14110819, 14111621), NTU Start-Up Grant (021337-00001).

Language: Английский

Citations

24
Recognition Engineering-Mediated Multichannel Sensor Array for Gut Microbiota Sensing DOI
Zhihui Liu, Xiaohua Zhu, Qiujun Lu

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(14), P. 5911 - 5919

Published: March 28, 2023

The composition and activity of the gut microbiota are crucial for health management disease treatment. Herein, we develop a rapid robust multichannel sensor array via recognition engineering strategy using antimicrobial agent (vancomycin, bacitracin, lysozyme) functional gold nanoclusters gluconamide-modified Ti3C2 MXenes, which provide superior fingerprint patterns to distinguish gut-derived bacteria. discrimination ability was highly improved synergistic between bacteria various agents. Five bacteria, including probiotics, neutral, pathogenic were clearly differentiated discriminated from mixtures. Furthermore, sensing system successfully applied accurate classification human colorectal cancer samples healthy individuals rapidly (30 min) with clinically relevant specificity. rapidity, simplicity, economic cost this offers platform analysis.

Language: Английский

Citations

23