搜索结果：Gut microbes

The gut harbors diverse community of microorganisms collectively known as the gut microbiota, which has important roles in health and disease, both within the gut and in distant tissues. In the healthy gut, physical, chemical/biochemical, and immunologic barriers confine these microbes to the gut lumen, and accordingly, the translocation and dissemination of live gut bacteria has been almost universally viewed as a pathologic process. However, recent studies suggest that in early life, there may also be physiologic translocation and dissemination of select live gut microbes that confer beneficial effects on the host. Here, we provide an overview of the translocation and dissemination of gut microbes in everyday life, disease settings, and early life, particularly noting how microbial translocation may foster beneficial outcomes in health and disease.

Bacteroides spp. are a key immune-programming microbe in healthy individuals-these bacteria have been shown to be reduced in abundance across a variety of disease states. Our study investigated the systemic and region-specific responses to Bacteroides colonization in the gut, including sex-related differences, in mice. Utilizing C57BL/6 mice, we administered Bacteroides to conventional, antibiotic-treated mice, then assessed this microbe's influence on the gut microbiota composition and inflammatory responses following an airway lipopolysaccharide challenge to assess effects on the gut-lung axis. We found that Bacteroides successfully colonizes the intestinal tract of antibiotic-treated mice, particularly the colon lumen of the large intestine, as evidenced by 16S rRNA amplicon gene sequencing and culturing. Differential gene expression analysis using NanoString technology revealed significant immune response variations across the gut regions, with notable differences in adaptive immune response genes. A striking sex-dependent outcome was noted in the regulation of atg12 in the cecum, potentially enhancing autophagic function, particularly in female mice. Additionally, Bacteroides intestinal colonization was associated with altered expression of macrophage markers such as cd163, cd84, and ms4a4a, which may reflect shifts in the macrophage profile within the cecum. These findings pave the way for novel therapeutic approaches that leverage microbial impacts on gut and systemic health, offering a deeper understanding of Bacteroides' role in human health and disease. Our study highlights the necessity for further research to elucidate the intricate relationships between gut microbiota, host immunity, biological sex, and their interplay. This research marks an investigation into how specific microbiota, like Bacteroides, regulate host responses across different gut regions to influence systemic health. By dissecting the impact of Bacteroides across multiple regions of the intestinal tract, this study offers new insights into the localized and whole-body effects of this important immune-programming microbe. Such an understanding is crucial as it helps in unraveling the complex interplay between gut microbes and the host's immune system. This research helps bridge the gap between local intestinal ecology and overall systemic health, addresses important questions relevant to the gut-lung axis, and helps pave the way for innovative therapies.

Background: The prevalence of neurodegenerative diseases like Alzheimer's and mental disorders like depression or anxiety appears higher in patients with gastrointestinal tract diseases like inflammatory bowel disease (IBD). Conversely, depressed patients have higher rates of gastrointestinal disorders. These observations suggest bidirectional communication between the brain and the gastrointestinal tract, the so-called "gut-brain axis". Moreover, an altered microbiota, called "dysbiosis", has been reported in these diseases, highlighting the network between gut microbes and their host. The emergence of the microbiota as a key regulator of the gut-brain dialog has led to the establishment of the concept of the "microbiota-gut-brain axis". Objectives: In this narrative review, we outline the main interaction channels between the gastrointestinal tract and the brain. Then, we summarize current knowledge of two major diets (i.e., Western and Mediterranean diets) and the principal dietary components that modulate the microbiota-gut-brain axis to discuss the mechanisms putatively involved in intestinal, psychiatric, and neurological disorders. Conclusions: Diet is a major factor influencing the gut microbiota, and consequently, also putatively systemic mechanisms through the microbiota-gut-brain axis. Indeed, the composition of the diet is crucial for health and disease. Despite the main role of diet, the physiological, cellular, or molecular mechanisms involved in the complex communication between the microbiome, gut, and brain are still poorly understood.

Myocardial ischemia-reperfusion injury (MIRI) remains a major complication. Fusobacterium nucleatum (F. nucleatum), an oral pathobiont associated with cardiometabolic disease, may influence host physiology by reshaping gut microbial function through an oral-gut axis. Whether such microbial interactions contribute to MIRI remains unclear. An oral F. nucleatum gavage mouse model and cohorts were established to investigate the effect of oral F. nucleatum on MIRI, gut microbial histidine metabolism including imidazole propionate (ImP) production, the association of ImP with coronary heart disease (CHD), and its microbial sources. MIRI was induced with or without antibiotic-mediated microbiota depletion and/or ImP administration, and p62 dependence was examined by knockdown approaches in vitro and in vivo. Plasma metabolites, cardiac injury, ultrastructure, and p62/mTOR signaling were assessed. F. nucleatum aggravated MIRI despite the absence of persistent colonic colonization. Instead, F. nucleatum altered gut microbial composition, including Lactobacillus abundance, and was associated with elevated circulating ImP. Antibiotic-mediated microbiota depletion reduced ImP and attenuated myocardial injury. Plasma ImP was elevated in patients with CHD, and ImP-producing capacity was supported primarily by gut microbiota urocanate reductase (UAR)-associated functions. In H9c2 cells, ImP exacerbated hypoxia/reoxygenation injury, and increased the autophagy adaptor p62 together with downstream mTOR/S6K1 signaling. p62 knockdown attenuated the mTOR/S6K1 response and injury-associated changes, whereas IRS1 suppression persisted. F. nucleatum reshapes gut microbial metabolism, thereby amplifying MIRI via ImP. ImP emerges as a functional mediator linking oral dysbiosis to MIRI, and reducing microbiota-derived ImP may represent a more mechanistically grounded strategy to mitigate MIRI. Oral pathobionts can aggravate MIRI by reshaping gut microbial metabolism via an oral–gut axis.Fusobacterium nucleatum is associated with gut urocanate reductase-positive microbial function, elevated circulating imidazole propionate (ImP).ImP activates p62/mTOR/S6K1 and reduces IRS1, with autophagy changes.

Low back pain is a leading cause of disability worldwide, and lumbar intervertebral disc degeneration (IVDD) is strongly associated with its development. Recent studies have shown that the gut microbiota (GM) and its metabolites may be involved in the occurrence and development of IVDD through the gut-disc axis. However, the key microbes mediating this process and their specific molecular mechanisms remain unclear. This study aimed to identify the gut microbes that play a key role in the progression of IVDD using multi-omics approaches and clarify the specific mechanisms by which these microbes participate in IVDD by regulating host cell functions. A single center, prospective cross-sectional study. We prospectively included 113 patients who underwent surgical treatment for symptomatic lumbar degenerative diseases from May 2022 to May 2023, and their degenerated lumbar intervertebral disc (IVD) tissues as well as paired feces samples were collected. Metagenomic next-generation sequencing (mNGS), modified Pfirrmann typing, Single-cell RNA sequencing (scRNA-seq), Bulk RNA sequencing (Bulk RNA-seq). Clinical IVD samples and paired fecal samples were prospectively collected and subjected to multi-omics bioinformatics analysis. mNGS was used to analyze the microbial composition in IVD and paired fecal samples. scRNA-seq was employed to resolve the cellular heterogeneity of IVD tissues. Bulk RNA-seq was utilized to identify the characteristics of host response genes related to microbial exposure. Subsequent AUCell scoring was performed to evaluate the abundance of microbes in cell subsets. The CellChat algorithm was applied to analyze the microbe-mediated intercellular communication network of host cells. The raw detection rate of mNGS in IVD tissues was 100%, with a positive rate of 60.2% (68/113) after excluding background bacteria. A total of 505 genera and 1,528 microbial species were detected, with dominant species including Stutzerimonas stutzeri and Moraxella osloensis. The mNGS detection rate in fecal samples was 100% (322 genera and 789 species), among which Phocaeicola vulgatus (PV) was a dominant species. A total of 7 bacterial species shared by GM and IVD were identified; however, only the relative abundances of PV and Bacteroides thetaiotaomicron (BT) increased gradually with the severity of IVDD. Single-cell RNA-seq identified 10 cell clusters, annotated as chondrocytes, macrophages, fibroblasts, and endothelial cells, with the proportions of the latter three non-chondrocyte populations being significantly higher in the severe IVDD group. Chondrocytes were further divided into subsets. Subsets MDC1 and MDC5 were related to mild degeneration with high expression of ACAN and SOX9, whereas SDC2, SDC3, SDC4, SDC6, and SDC7 were related to severe degeneration. AUCell scoring revealed that PV showed a significantly higher abundance in these pathological subsets, while BT was evenly distributed. Furthermore, chondrocytes with high PV abundance significantly upregulated matrix degradation genes including MMP13 and COL1A1, as well as cell adhesion genes such as POSTN and SPARC. These upregulated genes were significantly enriched in LPS-associated inflammatory cascades, extracellular matrix degradation, and metabolic reprogramming pathways. Crucially, LPS signaling genes including TLR4, MYD88, NFKB1, and RELA were upregulated in chondrocytes with high PV abundance, while short-chain fatty acid receptor genes were minimally expressed with no significant group differences. Finally, CellChat analysis revealed that high PV abundance amplified the communication between chondrocytes and macrophages, fibroblasts, and endothelial cells, which was mediated by the CXCL pathway for immune recruitment, the VEGF and ANGPT pathways for angiogenesis, and the TGF-β pathway for pro-fibrotic remodeling. This study suggests that gut-derived PV may activate the inflammatory response of chondrocytes through the LPS-mediated TLR4-MYD88 signaling axis and reshape the intercellular communication network, thereby potentially contributing to the process of IVDD. These findings provide novel mechanistic insights into the gut-disc axis theory and offer new perspectives on IVDD therapeutic strategies targeting microbe-host interactions.

Gut bacteria produce a wide variety of metabolites that are playing important roles in human health. Dietary fibres (DF) are beneficial nutrients that have been shown to modulate key intestinal functions when fermented by gut bacteria. Since most bacteria-derived metabolites are volatile, their presence in exhaled breath allows to propose new non-invasive methods to study DF-microbiome interactions in humans. We aimed to identify potential novel biomarkers of gut microbiota activity released in exhaled breath following the consumption of DF at breakfast, upon untargeted analysis in healthy volunteers. 14 volunteers (7 women/7 men, 21 ± 2 years old) participated to two test days at a one-month interval, where they received either a low-(2.6 g) or high-(16.1 g) fibre breakfast. Before each test days, stools were collected to evaluate the microbiota composition using Illumina sequencing (V5-V6 region of 16S rRNA gene). Throughout the test days, breath samples were analysed using selected-ion flow-tube mass spectrometry (SIFT-MS). A sparse partial least squares-discriminant analysis (sPLS-DA) identified 30 signals that best discriminated between test days, corresponding to 173 candidate breath compounds. The gut microbiota of the volunteers remained stable one month apart. The composition of exhaled breath shifted starting from 5 h after the high-fibre breakfast ingestion. Ninety compounds were identified as potential metabolites of gut microbes, with 81 showing increased concentrations after the high-fibre breakfast. These included acrylic acid (positively correlated with Faecalibacterium/Ruminococcaceae/Bacillota and negatively correlated with Bifidobacterium/Bifidobacteriaceae/Actinomycetota). The high-fibre breakfast also led to increases in limonene, ethylbenzene/xylene, p-cymene, and methionol that were positively correlated with the genus Faecalibacterium. Moreover, positive correlations were observed between cyclooctane/ethylcyclohexane, methanol and the phylum Bacillota. Dimethyl disulfide was strongly negatively correlated with the genus Bacteroides and its family Bacteroidaceae. This study shows that DF consumption at breakfast stimulates the production of exhaled bacteria-derived metabolites reflecting profound changes in the metabolic activity of the gut microbiota. We also identified new potential biomarkers of DF intake, that are not directly linked to DF fermentation. Specific bacteria known to play a role in gut barrier, immunity and host metabolism were associated with those new metabolites.

Sexual dimorphism and mode of delivery are key determinants of gut physiology and microbiota development and may differentially affect predisposition to gut-related diseases. Cesarean section delivery markedly shapes early-life microbiota, predisposing individuals to higher risk of immune and metabolic comorbidities later in life. Although both sex and delivery mode are known to influence gut barrier-microbiota crosstalk, whether delivery mode modulates or counter-regulates sex-specific features of this interaction remains, to our knowledge, largely unexplored. Here, we investigated how sex impacts gut barrier-microbiota crosstalk shaped by delivery mode across development until adulthood by reanalyzing existing data. Using a preclinical mouse model, we combined gut barrier analyses with differential abundance and co-occurrence network approaches (LinDA and NetMoss). We found that the impact of CSD on gut barrier-microbiota crosstalk is partially dependent on sex and life stage. During the first days of life, delivery mode dictates immune imprinting and microbial network topology, with only limited sex effects. However, trajectories diverged with age, with CSD males exhibiting colitis reoccurrence in adulthood. By applying integrative strategies to stratify data by sex and development, our study uncovers short- and long-term sex-dependent gut barrier and microbial signatures. These findings reveal that delivery mode might program sex-specific host-microbiota trajectories with consequences for gut health and disease susceptibility, highlighting the need to consider sex and early-life microbial imprinting in future microbiome-targeted interventions.

Phocaeicola vulgatus is one of the most ubiquitous and abundant bacterial members of the human gut microbiota; however, the genetic factors that are essential for its survival and persistence in the mammalian gut and in a colitic host have not been analyzed. Using both RB-TnSeq and transcriptomic analyses, we performed genome-wide, unbiased analyses to identify genes important for growth in rich medium, those contributing to gut colonization, and those important during dextran sulfate sodium (DSS)-induced colitis. RB-TnSeq analyses of P. vulgatus from the feces of monocolonized mice identified 1189 genes that contribute to fitness in the gut. Transcriptomic analysis showed that the alternate sigma/anti-sigma factor gene pair ecfO-reo and the nigD genes of its regulon are amongst the most highly expressed genes in the mono-colonized mouse gut. Analyses of genes important during DSS-induced colitis identified a distinct set of genes, many of which are involved in nutrient acquisition. We extensively studied several genes affecting fitness by deletion mutant analysis with subsequent phenotypic characterization and by mouse competitive colonization analyses. Finally, we identified a previously undescribed sigma/anti-sigma factor pair that is drastically upregulated during DSS-induced colitis, along with a co-transcribed spy chaperone gene, known to help protect bacteria against numerous stressors. Altogether, this study provides the first comprehensive genome-wide analysis of P. vulgatus from the mouse gut and of any gut Bacteroidales strain during colitis.

Severe acute malnutrition (SAM) is a leading cause of childhood morbidity and mortality that is defined by anthropometric measurements, weight-for-height z score, and mid-upper arm circumference (MUAC) falling significantly below healthy standards. While treatments for SAM and our understanding of this disease have advanced, children experiencing SAM frequently relapse to acute malnutrition (AM) following anthropometric recovery. Little is known about the contribution of the gut microbiome to AM relapse. We hypothesized that features of the gut microbiome, including microbial composition, antimicrobial resistance gene carriage, and predicted microbial functional pathways, of children discharged from treatment for uncomplicated SAM in South Sudan, may be associated with AM relapse at 1-month follow-up. Overall, broad microbiome profiles at discharge were not associated with AM relapse. We evaluated the associations of microbiome features with AM relapse 1-month post-recovery using mixed linear effect models. We identified associations between higher MUAC, which may be a proxy for future health trajectories, and increased Sutterella wadsworthensis and trimethoprim-resistant dihydrofolate reductase antimicrobial resistance genes. These findings suggest that the gut microbiome at discharge of children treated for uncomplicated SAM has limited predictive value as a standalone diagnostic tool for identifying relapse risk at 1 month.IMPORTANCESevere acute malnutrition (SAM) is a devastating illness that impacts the morbidity and mortality of millions of children worldwide. Community-based management of acute malnutrition (CMAM) is the standard of care in South Sudan and many other low-resource settings for children presenting with SAM. Despite this intervention, children treated for SAM under CMAM frequently relapse to acute malnutrition (AM) following treatment. With advancements in our understanding of malnutrition, there has been a strong and growing interest in developing microbiome-based strategies to treat, prevent, and predict relapse to AM following treatment for SAM. Our work characterizes gut microbiome features of children from a geographic area that is traditionally underrepresented in gut microbiome research and shows that in isolation, a child's gut microbiome at discharge likely holds low predictive value for relapse to AM post-CMAM treatment; however, we identified key microbes and microbial features meriting further research.

The oral-gut axis links the oral and gut microbiomes, both anatomically and functionally, and its dysregulation is implicated in periodontitis and inflammatory bowel disease (IBD). Bacterial extracellular vesicles (BEVs), nano-sized particles (20-250 nm) released by diverse microbes, serve as key mediators of inter-organismal communication along this axis. Carrying virulence factors, nucleic acids, and immunomodulators, BEVs influence microbial ecology and host immunity. In the oral cavity, pathogen-derived BEVs (e.g., from Porphyromonas gingivalis) promote biofilm formation, immune evasion, and tissue destruction. In the gut, BEVs from commensals (e.g., Akkermansia muciniphila) reinforce barrier function and suppress inflammation, whereas those from pathogens exacerbate dysbiosis. Critically, BEVs mediate bidirectional crosstalk: oral pathogen BEVs can translocate to the gut and worsen IBD, while beneficial gut-derived BEVs may attenuate periodontal inflammation. This review summarizes the roles of BEVs in oral-gut communication, their involvement in inflammatory disease pathogenesis, and their potential as biomarkers and therapeutics.

Purpose: Survivorship in colorectal cancer (CRC) is often accompanied by co-occurring psychoneurological symptoms (PNS, e.g., fatigue, depression, pain), which negatively affect quality of life. Caregivers of individuals with CRC also experience PNS due to caregiving burdens, amplifying distress across the dyad. PNS may be influenced by the activity of the gut microbes. The purpose of this pilot study was to examine gut microbiome diversity and composition, and their association with PNS in CRC patients and their caregivers. Methods: Baseline data from a technology-based dyadic intervention were included in this analysis. Eleven patients and eight caregivers provided stool samples and completed PROMIS measures of PNS at baseline. Gut microbiome profiles were assessed using 16S rRNA gene sequencing. Alpha and beta diversity metrics and differential abundance analyses were used to characterize the gut microbiome and examine its associations with PNS. Results: Patients exhibited significantly lower microbial alpha diversity than caregivers in the full sample (p = 0.033). Dyadic comparisons identified 92 differentially abundant taxa, with patients showing depletion of short-chain fatty acid-producing taxa and enrichment of opportunistic taxa. Microbiome-symptom models revealed significant interactions by group (patient vs. caregiver) and taxa-level effects, with patients showing stronger positive associations between microbial alterations and higher PNS severity. Conclusions: CRC patients actively on chemotherapy demonstrated reduced diversity and depletion of beneficial taxa that may contribute to heightened PNS. Caregivers, despite healthier profiles, reported substantial symptom burden that were linked to gut microbiome features, highlighting dyadic interdependence and the potential for microbiome-targeted, dyadic interventions in survivorship care.

Probiotics are commonly applied to maintain the balance of gut microbiota and regulate the intestinal metabolic function of companion animals. In the present study, complex probiotics (Bacillus coagulans SNZ-1969, Bacillus subtilis, and Bacillus licheniformis) were added into the basal diet of domestic cats to investigate their influence on the intestinal microbiome and metabolic characteristics. Results revealed that the alpha diversity of the gut microbiota in the probiotic group was enhanced when compared to the control group. The beta diversity of the gut microbiota was also altered by the oral consumption of the complex probiotics. Compared to the control group, the relative abundance of beneficial microbes (such as Clostridium, Bacteroides, Phocaeicola, and Ruminococcus) in the probiotic group was enhanced, while the relative abundance of opportunistic pathogens (such as Escherichia, Gallibacter, Corynebacterium) was decreased. Additionally, the intestinal metabolic characteristics of domestic cats were also changed. The metabolomic analysis identified 408 differential metabolites between the two groups, and the KEGG function pathway analysis proved that the dominant pathway related to the differential metabolites were the amino acid metabolism, lipid metabolism, carbohydrate metabolism, energy metabolism, endocrine system, digestive system, immune system, and other metabolic pathways. Spearman's correlation analysis revealed that the beneficial microbes had positive correlations with the differential metabolites. In conclusion, the current study demonstrated that oral administration of complex probiotics could regulate overall health and well-being in domestic cats through modulating the gut microbiome and metabolic characteristics.

Sickle cell disease (SCD) is a chronic, inherited condition rising across the globe. Prior studies revealed a direct link between the gut microbiome and disease micropathology via aged-like (ANs) neutrophils in mouse models. In SCD patients community-level shifts in the gut microbiome included decreases in diversity and the Firmicutes/Bacteroides (F:B) ratio, coupled to a loss of short chain fatty acid producing microbes and a shift to non-canonical butyrate production and aerobic fatty acid oxidation pathways. ANs and the proviral microbiome associate with multiple blood cytokines, while bacterial gut microbiome features largely do not. Prophages depleted of genes related to lysis, transcriptional regulation, and host takeover were enriched in SCD patient guts, pointing to domestication of these elements, and 25% of prophages were shared at high identity between study patients. In sum, we identify a viral-immune axis in SCD pathophysiology and targetable functional alterations to the gut microbiome in a heterogeneous chronic disease both affected by and effecting microbiome composition and function.

Dysbiosis of the gut microbiota is a key driver in the onset and persistence of inflammatory bowel disease (IBD). However, the mechanisms by which microbes influence mucosal immunity via specific epithelial routes remain incompletely elucidated. Microfold (M) cells within follicle-associated epithelium serve as a critical "gateway" for luminal antigens and microbes to access the mucosal immune system. While essential for surveillance of commensal microbes, M cells could also be exploited by adherent-invasive strains and adverse environmental factors to amplify inflammation. Recent studies suggest that both in Crohn's disease and ulcerative colitis, M cell abundance and function are aberrantly regulated, linking microbial imbalance with heterogeneous mucosal inflammatory phenotypes. Traditional animal models and two-dimensional culture systems retain limited capacity to selectively manipulate M cells without perturbing systemic immunity, thereby constraining systematic studies of microbiota-M cell co-cultures. Advances in intestinal organoid technology now enable controlled induction of functionally mature M cells within three-dimensional epithelial structures, and have started to shed light on the roles of RANKL signaling, negative regulators, and microbe-associated factors in M cell differentiation and homeostasis. In this review, we focused on key evidence supporting microbiota-M cell interactions in IBD, discussed how M cell-enriched intestinal organoid models could be leveraged to dissect the impact of pathogenic microbes, candidate probiotics, dietary components, and existing therapies on these interactions as well as to evaluate the related potential and limitations for microbiome interventions and drug screening. Integrating gut microbial plasticity with M cell epithelial entry and organoid platforms promises to provide new experimental foundations and theoretical support for individualized microbiome-based therapies and targeted mucosal treatments in IBD.

The Developmental Origins of Health and Disease theory describes early life as a critical window for long-term metabolic health. Accumulating evidence has identified the gut microbiota as a key mediator of early-life metabolic programming. This study utilized antibiotic intervention in neonatal mice to investigate the long-term effects of early postnatal gut microbiota perturbations on adult lipid metabolism and examined the underlying mechanisms involving both thermogenic adipose tissue programming and microbiota structural remodeling. We found that early postnatal antibiotic exposure significantly disrupted the normal developmental assembly of the gut microbiota. Surprisingly, these alterations were associated with partial attenuation of high‑fat diet‑induced lipid metabolic disturbances in adulthood, an effect that was more pronounced in male mice than in female mice. Mechanistically, the observed metabolic improvement appeared to be associated with brown adipose tissue (BAT) thermogenic activation rather than with white adipose tissue browning or persistent gut microbiota restructuring. Early postnatal antibiotic exposure-associated gut microbiota alterations were linked to enhanced BAT development, potentially via interleukin-6 signaling and M2 macrophage polarization, suggestive of a metabolic programming effect that enhanced adaptive thermogenesis and improved long-term lipid homeostasis. These findings indicate that the gut microbiota might represent a modifiable factor influencing adipose tissue development, highlighting the potential of targeting the microbiota-BAT interplay in early life for obesity prevention strategies.

Placental biology is increasingly framed through a signaling paradigm in which maternal microbiome-derived mediators-rather than microbial colonization-affect the function of the interface. This review synthesizes evidence that circulating microbial signals, including short-chain fatty acids, tryptophan-derived indoles, bile-acid-linked ligands, microbe-associated molecular patterns, and bacterial extracellular vesicles, are associated with placental vascular development, immune regulation, nutrient transport, and endocrine programs-processes central to pregnancy outcomes. We integrate mechanistic insights from gnotobiotic and supplementation models with limitations of human evidence and identify key translational gaps. The current evidence supports a model in which maternal microbial ecology shapes a network of circulating mediators that converge on interlinked placental pathways essential for placental function and fetal development.

Heart failure (HF) management remains challenging because patients often show large differences in how well treatments work and in how often adverse drug reactions occur. Traditional pharmacogenomics cannot fully explain these differences. Emerging evidence from pharmacomicrobiomics shows that the gut microbiome represents a previously underappreciated factor influencing drug responses. This review summarizes the two-way interactions between the gut microbiota and key HF drugs, including digoxin, angiotensin receptor-neprilysin inhibitors (ARNIs), ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRAs), and diuretics. On the one hand, gut microbes can change drug effects because they can metabolize drugs and affect host physiological pathways. On the other hand, HF drugs can change the structure and function of the gut microbial community. This review also discusses how microbiome-related features may serve as biomarkers to support personalized treatment and how strategies such as dietary changes and microbiota-targeted therapies may improve clinical outcomes. Although evidence remains limited, and certain methods require further refinement, integrating microbiome insights into HF treatment may support more precise and individualized treatment strategies and help address current therapeutic limitations.