iMeta, Год журнала: 2024, Номер unknown
Опубликована: Дек. 31, 2024
Accumulating evidence indicates that the gut microbiota is intricately involved in initiation and progression of human diseases, forming a multidirectional regulatory axis centered on intestinal microbiota. This article illustrates challenges exploring role inflammatory digestive such as metabolic dysfunction-associated steatotic liver disease (MASLD) bowel (IBD), summarizes existing microbiome-focused treatment strategies (probiotics, prebiotics, symbiotics, fecal transplantation, bacteriophages therapy), emerging technologies (gut microbiome-on-a-chip artificial intelligence), well possible future research directions. Taken together, these therapeutic present both opportunities challenges, which require researchers clinicians to test rationality feasibility various modalities continuous practice. To Editor, The gastrointestinal tract accommodates diverse range microbes, including bacteria, fungi, viruses, archaea, jointly regulate host metabolism, immune responses, redox homeostasis, by producing active substances lipopolysaccharide (LPS), trimethylamine, polysaccharides, endogenous alcohol, short-chain fatty acids (SCFAs), secondary bile [1, 2]. A wealth preclinical clinical has manifested substantial microbes their metabolites developing progressing diseases. These studies have deepened our comprehension etiology contributed novel targeting However, it important recognize diseases represents challenge an opportunity, with several key issues impeding progress field merit attention. In this perspective, we illustrated summarized strategies, technologies, development non-culture techniques for multi-omics sequencing technology understanding how influences health disease. Numerous convincingly show microbiological profiles patients differ significantly from those healthy individuals, variations spanning all taxonomic levels. consensus emerged regarding certain structural characteristics at phylum level. finer levels, microbiome compositions exhibit considerable heterogeneity contradictory findings across studies, presenting significant current research. underlying reasons phenomenon are manifold, encompassing factors differences platforms regions, statistical biases, timing sample collection [3], microbial load [4], detailed Table 1. Collecting large multi-center cohort will be effective strategy address data heterogeneity, confounding variables mentioned 1 should also fully considered experimental design. Additionally, establishing minimum quality control standards design, collection, analysis must thoroughly enable integration within standardized framework. Gut microbiota-derived molecular mediators microbiome-host interaction maturation, mucosal integrity [5]. Advances mass spectrometry, data, illuminating contribute pathogenesis incomplete metabolomic remains major predicament, not only reflected scarcity conditions like primary sclerosing cholangitis (PSC) acute pancreatitis (AP) but uncertainty metabolite function. For instance, while SCFAs generally regarded beneficial Wang et al., recently demonstrated butyrate propionate bacterially derived danger signals promote interleukin-1beta (IL-1β) release through epigenetic regulation activating nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR), pyrin domain-containing protein 3 (NLRP3) macrophages [6]. transnational cohorts may assist providing more light microbe-derived affect phenotypes. addition, innovative methods detecting unknown compounds, especially low concentrations samples, need developed further advance known unknown, breaking limitation knowledge framework studies. harbors rich diversity protozoa. Currently, majority focused alterations bacteria influence largely neglecting mycobiome virome elements, appropriately described "dark matter" context reality, eukaryotes, possess genomes about 100 times larger than display greater biological complexity, hold influencing [7]. Similarly, viruses gut, bacteriophages, act natural bacterial predators instrumental maintaining ecological community [8]. Future thus strengthen study two matters" disease, particularly emphasizing evolutionary biology comprehensive databases. resource competition selection pressure engendered activity among microorganisms give rise interactions between fungi or viruses. How fascinating area. Recent revealed 3-succinylated cholic acid, lumen-restricted acid produced Bacteroides uniformis, can alleviate MASLD promoting growth Akkermansia muciniphila [9], exemplifies typical cross-feeding pattern. reduction absence mutual feeding resources likely contributes deterioration, merely one "trade route" numerous interactions. Therefore, reprogramming complex networks could pivotal treating ameliorating principle widely applicable microbiome-related conditions. Unfortunately, limited, mostly confined association analyses without empirical validation, area requires reinforcement. Identifying reliable biomarkers crucial significance diagnosing contrast invasive colonoscopy, gold standard IBD, biomarker identification early detection prediction, facilitate timely interventions, reduce risk complications [10]. Nevertheless, undermines its reliability reproducibility diagnostic biomarker. Encouragingly, recent offered promising solutions. Zheng multibacteria panel, included enriched depleted species, delivered excellent performance distinguishing IBD non-IBD, Crohn's (CD) ulcerative colitis (UC) different regions ethnicities [11]. method effectively mitigates bias other often hinder cross-sectional Furthermore, given relationship status, genetics, integrating metagenomic recommended identify robust using large-scale datasets. It emphasize any outperform currently use maintain independent cohorts. Increasing indicated dysregulation associated Manipulating approach gut-derived primarily replenishing anti-inflammatory metabolites, eliminating pathogenic restoring entire ecosystem. Current comprise probiotics, transplantation (FMT), (Figure 1). randomized trial FMT phenotype nonalcoholic (NAFLD, MASLD's former name) improving imbalance microbiota, efficacy was higher lean NAFLD obese [12]. finding underscores potential suggests effectiveness vary depending subtypes. note still few blinded controlled trials. attributed broad nonspecific nature FMT, provides scant information long-term effects individuals raises concerns safety. When treat precise matching donor recipient strictly implemented, similar blood type organ matching, ensure most outcome. remodeling homeostasis varies influenced properties baseline abundance opportunistic pathogens, degree functional redundancy, stage [13]. Colonization resistance, where colonizes tissue exclude pathogen infection (whether resident invasive), factor [14]. years, utilizing specifically target attracted extensive attention precision medicine approach. As phages thrive environments exist. Viral particles vastly outnumber over 90% being phages. Intestinal adults predominantly individual highly diverse, crAss-like Microviridae stable colonizers, affecting [15]. Cornuault JK discovered Faecalibacterium prausnitzii compared mild stool samples [16]. offers new avenue microbiota-mediated "post-antibiotic era," narrow levels disturbing surrounding Within theoretical framework, phage mixtures common alcoholic (ALD), MASLD, PSC, based dominant [17]. shown animal small therapy stages. addition laws regulations, addressed, dose determination, lysis-induced localized inflammation, pharmacokinetic pharmacodynamic properties. More fundamental well-designed randomized, blinded, placebo-controlled trials requisite field. resurgence stimulated phage-related endolysin drug candidate great potential. Phage endolysins cell wall hydrolases encoded during late replication enzymes peptidoglycan wall, leading rupture death. precisely pathogens eradicate biofilms, dilemma antibiotics difficulty disease-causing biofilms [18]. computational biology, bioinformatics, synthetic usher dawn treatment. Technological innovations breakthroughs brought forth horizons Lee proposed scalable (GMoC) reproducible 3D stratified epithelium Caco-2 cells, visualize behavior collective high-magnification imaging [19]. technique efficient biomimetic scaffold cultivating studying discover targets mechanisms induce therapies. intelligence (AI), driven cutting-edge algorithms machine learning, deep learning models, neural networks, generative graphical processing units, interpretable revolutionizing diagnosis [20]. ecosystem characterized dynamic microbe–microbe, host–microbe, microbe–environment Integrating multiple AI models efficiently manage interpret datasets, temporal spatial network. facilitates prediction response, monitoring activity, progression, recurrence. application confronts related quality, reproducibility, universality, ethical, legal, use. continues evolve intersection practice, imperative rigorous conducted evaluate benefits. Exploring niche changes insights into variables, ubiquitous population multicenter solving some rare relying advantage quantity becomes difficult. Meanwhile, design experiments cohorts, alongside strengthening integrated better combined elucidate regulation. microbial-based Yongpeng Shi: Writing—original draft; writing—review editing. Zeran Chen: Tingyu Fang: Xingyao draft. Youpeng Deng: Hao Qin: Min Lian: Juntao Shen: Yuru Zong: Huikuan Chu: Constanze Hoebinger: Guo: Writing—review Zhongshang Yuan: Jie Zheng: Yongjian Zhou: Yue Pan: Beatriz G Mendes: Sonja Lang: Tim Hendrikx: Suling Zeng: Hailong Cao: Ling Yang: Lianmin Peng Lei Dai: Hua Wang: Shi Yin: Shu Zhu: Xiong Ma: Bernd Schnabl: Hanqing Project administration; conceptualization; supervision; editing; funding acquisition. Yi Duan: Conceptualization; project work supported Postdoctoral Fellowship Program CPSF (No. GZC20232554), Fundamental Research Funds Central Universities WK9100000083), China Science Foundation 2024M753097), Nation Natural Qin 32301202), NIDDK-funded San Diego Digestive Diseases Center P30DK120515), NIAAA-funded Southern California ALPD Cirrhosis Schnabl P50AA011999), 32171370), Beijing L248075), Scientific Innovation Academy Chinese Medical Sciences CI2023C012YL), Guangdong Province Chen 2022A1515010415), Advanced Interdisciplinary Biomedicine IHM QYPY20230033), WK9100000063), Strategic Priority Duan XDB0940000). been consulting Ambys Medicines, Ferring Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Surrozen Takeda. Schnabl's institution, UC Diego, received support Axial Biotherapeutics, BiomX, ChromoLogic, CymaBay Intercept, NGM Biopharmaceuticals, Prodigy Biotech Synlogic Operating Company. founder Nterica Bio. filed patents Duan, Lang, inventors work. authors declare no conflict interest. No animals humans were study. Data sharing created analyzed paper does generate data. Supplementary materials (graphical abstract, slides, videos, translated version, updated materials) found online DOI iMeta http://www.imeta.science/.
Язык: Английский