Unified Interpretations of Two Kinds of Needle-Shaped Precipitates Using Transmission Electron Microscopy and Small-Angle Neutron Scattering in Aged Al-Mg2Si(-Cu) Alloys.

This study investigates the nanostructural properties of pseudo-binary Al-1.0Mg2Si (mass%) alloys with and without 0.5Cu using transmission electron microscopy (TEM) and small-angle neutron scattering (SANS). The TEM results show that both alloys exhibit extra electron diffraction spots related to MgSiMg second clusters at peak-aged conditions. High-resolution TEM images have revealed that the second cluster exists as a needle-shaped precipitate that is shorter and thicker than the ß″ phase. We found that the second cluster, which we referred to as the R phase in this paper, is more likely to form partially along the longitudinal axis of a random-type precipitate. Thus, the atomic arrangement in the random-type precipitate is not completely random. SANS is used to quantify the size and volume fraction of the observed needle-shaped precipitates since the R phase is difficult to observe with TEM. The R phase forms even in the Cu-free alloy, but the volume fraction is low, and the growth and formation are retarded near the peak-aged conditions. Undoubtedly, the Cu addition has the effect of stabilizing the growth of the R phase and also promoting its formation. Therefore, the R phase also contributes to the increase in hardness at both under- and peak-aged conditions in the Cu-containing alloy in addition to the strengthening ß″ phases.

Intermittent hypoxia inhibits mandibular cartilage growth with reduced TGF-ß and SOX9 expressions in neonatal rats.

Intermittent hypoxia (IH) has been associated with skeletal growth. However, the influence of IH on cartilage growth and metabolism is unknown. We compared the effects of IH on chondrocyte proliferation and maturation in the mandibular condyle fibrocartilage and tibial hyaline cartilage of 1-week-old male Sprague-Dawley rats. The rats were exposed to normoxic air (n = 9) or IH at 20 cycles/h (nadir, 4% O2; peak, 21% O2; 0% CO2) (n = 9) for 8 h each day. IH impeded body weight gain, but not tibial elongation. IH also increased cancellous bone mineral and volumetric bone mineral densities in the mandibular condylar head. The mandibular condylar became thinner, but the tibial cartilage did not. IH reduced maturative and increased hypertrophic chondrocytic layers of the middle and posterior mandibular cartilage. PCR showed that IH shifted proliferation and maturation in mandibular condyle fibrocartilage toward hypertrophic differentiation and ossification by downregulating TGF-ß and SOX9, and upregulating collagen X. These effects were absent in the tibial growth plate hyaline cartilage. Our results showed that neonatal rats exposed to IH displayed underdeveloped mandibular ramus/condyles, while suppression of chondrogenesis marker expression was detected in the growth-restricted condylar cartilage.

Intermittent hypoxia retards mandibular growth and alters RANKL expression in adolescent and juvenile rats.

OBJECTIVES: Chronic intermittent hypoxia (IH), a common state experienced in obstructive sleep apnoea (OSA), retards mandibular growth in adolescent rats. The aim of this study was to elucidate the differential effects of IH on mandibular growth in different growth stages. MATERIALS AND METHODS: Three-week-old (juvenile stage) and 7-week-old (adolescent stage) male Sprague-Dawley rats underwent IH for 3 weeks. Age-matched control rats were exposed to room air. Mandibular growth was evaluated by radiograph analysis, micro-computed tomography, real-time polymerase chain reaction and immunohistology. Tibial growth was evaluated as an index of systemic skeletal growth. RESULTS: IH had no significant impact on the general growth of either the juvenile or adolescent rats. However, it significantly decreased the total mandibular length and the posterior corpus length of the mandible in the adolescent rats and the anterior corpus length in the juvenile rats. IH also increased bone mineral density (BMD) of the condylar head in adolescent rats but did not affect the BMD of the tibia. Immunohistological analysis showed that the expression level of receptor activation of nuclear factor-κB ligand significantly decreased (in contrast to its messenger ribonucleicacid level) in the condylar head of adolescent rats with IH, while the number of osteoprotegerin-positive cells was comparable in the mandibles of adolescent IH rats and control rats. LIMITATIONS: The animal model could not simulate the pathological conditions of OSA completely and there were differences in bone growth between humans and rodents. CONCLUSIONS: These results suggest that the susceptibility of mandibular growth retardation to IH depends on the growth stage of the rats.

Intermittent hypoxia induces turbinate mucosal hypertrophy via upregulating the gene expression related to inflammation and EMT in rats.

PURPOSE: Chronic intermittent hypoxia (IH) plays a pivotal role in the consequences of obstructive sleep apnea (OSA). It has been demonstrated that IH impairs nasomaxillary complex growth to reduce nasal airway cavity size in rodent models. Although turbinate dysfunction with inflammatory mucosal hypertrophy is related to OSA, the role of IH in turbinate hypertrophy with inflammation-driven fibrosis is unknown. Here, we aimed to clarify the pathogenesis of inflammatory mucosal hypertrophy and epithelial-mesenchymal transition (EMT) in the nasal turbinate under IH. METHODS: Seven-week-old male Sprague-Dawley rats were exposed to IH (4% O2 to 21% O2 with 0% CO2) at a rate of 20 cycles/h. RESULTS: Hypertrophy of the turbinate mucosa occurred after 3 weeks, with the turbinate mucosa of the experimental group becoming significantly thicker than in the control group. Immunostaining showed that IH increased the expression of TGFß and N-cadherin and decreased E-cadherin expression in the turbinate mucosa. Quantitative PCR analysis demonstrated that IH enhanced the expression of not only the inflammatory markers Tnf-a, Il-1b, and Nos2 but also the EMT markers Tgf-b1, Col1a1, and Postn. CONCLUSIONS: Collectively, these results suggest that IH induced turbinate hypertrophy via upregulation of gene expression related to inflammation and EMT in the nasal mucosa.

Development of a biaxial tensile testing machine for pulsed neutron experiments.

A biaxial tensile testing method has been used to get macroscopic information on elastoplastic deformation of a thin steel specimen and improve the accuracy of plastic processing of steel materials. We newly developed a biaxial tensile testing machine for pulsed neutron experiments (BTM-NEU) to provide the microscopic crystallographic information of steel materials under biaxial load and correlate it with the macroscopic mechanical properties of the materials. The performance of the BTM-NEU was experimentally evaluated with cold-rolled mild steel and hot-rolled high-tensile-strength steel materials and compared with that of a standard biaxial tensile testing machine (BTM-std) as follows. •The BTM-NEU can test an ISO-standardized cruciform specimen as the BTM-std and its performance is equivalent to that of the BTM-std.•The BTM-NEU has excellent long-time reliability and stability necessary for pulsed neutron experiments, especially Bragg-edge neutron imaging experiments.•The BTM-NEU can be applied to pulsed neutron experiments using a Bragg-edge imaging method.

Differential growth of craniofacial and tibial bones to sympathetic hyperactivity-related hypertension in rats.

OBJECTIVE: To evaluate the effect of sympathetic nervous system hyperactivity on craniofacial skeletal growth in growing spontaneously hypertensive rats (SHRs). DESIGN: Craniofacial skeletal growth was compared between male SHR and Wistar-Kyoto rats (WKR) using linear measurements on lateral and transverse cephalometric radiographs at the age of 12 weeks. Tibia length was measured as an index of whole body growth. Body weight　and blood pressure were measured from 3 to 12 weeks of age. Bone microstructure in the mandibular condyle and tibia between the two groups was compared at the age of 12 weeks using microcomputed tomography. RESULTS: The SHRs had a significantly lower body weight than WKRs from 7 weeks of age, and tibial length was significantly smaller in the SHRs than in the WKR at 12 weeks of age. In all SHRs, blood pressure was significantly higher than in WKRs from 3 to 12 weeks of age. Cephalometric analyses revealed decreased measurements of the neurocranium, viscerocranium, and mandible in SHRs, and mandibular growth was most negatively affected in this group. Lastly, in SHRs, microcomputed tomography analyses revealed decreased bone mineral density and bone volume/tissue volume in the mandibular condyle but not in the tibia. CONCLUSION: In growing SHRs, hypertension related to the hyperactivity of the sympathetic nervous system reduced craniofacial skeletal growth more than the growth of the tibia.

A novel IkB kinase inhibitor attenuates ligature-induced periodontal disease in mice.

BACKGROUNDS AND OBJECTIVES: IMD-0354 is a novel I kappa-B kinase (IKK) inhibitor, which regulates inflammation. The purpose of this study was to examine the effect of the reagent on bone loss for ligature-induced periodontitis. MATERIAL AND METHODS: We ligated around the upper right second molars of 8-week-old C57BL/6J mice in the split-mouth model. The test mice were injected intraperitoneally with IMD-0354 before the placement of the ligature. The control mice were injected intraperitoneally with 0.5% carboxymethylcellulose (CMC) as vehicle before the placement of the ligature. To determine the optimum concentration of the reagent on ligature-induced periodontitis in the mice, we examined the effect of three types of concentration, which were 1, 5, and 10 mg/kg of IMD-0354, as a preliminary experiment. After we determined 10 mg/kg as the optimum concentration for the IMD group by micro-CT analysis, both the IMD and CMC groups (n = 15 each in total, including all the analyses) were subdivided into two small groups, respectively, for further analyses: I group (unligated side of IMD group), IL group (ligated side of IMD group), C group (unligated side of CMC group) and CL group (ligated side of CMC group). The mice in the IMD and CMC groups were treated with each reagent daily and sacrificed 8 days after the ligation. For assessment of bone resorption, we performed micro-CT and histological analyses. We also carried out real-time PCR to investigate proinflammatory and bone metabolic markers. RESULTS: There were significant differences for linear bone loss and volumetric parameter in the test (IMD) group compared to the control (CMC) group 8 days after ligation. In terms of the mRNA expression level of gingival tissue, the level of RANKL was significantly suppressed in the IMD group compared to the CMC group. IMD-0354 also tended to suppress the levels of interleukin-1 beta, tumor necrosis factor-alpha, and osteoprotegerin. For histological analysis, the relative numbers of TRAP-positive multinucleated cells decreased significantly in the IMD group compared to the CMC group. CONCLUSION: IMD-0354 regulated bone resorption by ligature-induced periodontitis, and it is suggested that the inhibition of IKK via down-regulation of NF kappa-B may provide periodontal patients with an effective approach to prevent or suppress the disease.

Neutron scattering studies on short- and long-range layer structures and related dynamics in imidazolium-based ionic liquids.

Alkyl-methyl-imidazolium ionic liquids CnmimX (n: alkyl-carbon number, X: anion) have short-range layer structures consisting of ionic and neutral (alkylchain) domains. To investigate the temperature dependences of the interlayer, interionic group, and inter-alkylchain correlations, we have measured the neutron diffraction (ND) of C16mimPF6, C9.5mimPF6, and C8mimPF6 in the temperature region from 4 K to 470 K. The quasielastic neutron scattering (QENS) of C16mimPF6 was also measured to study the dynamics of each correlation. C16mimPF6 shows a first-order transition between the liquid (L) and liquid crystalline (LC) phases at Tc = 394 K. C8mimPF6 exhibits a glass transition at Tg = 200 K. C9.5mimPF6, which is a 1:3 mixture between C8mimPF6 and C10mimPF6, has both transitions at Tc = 225 K and Tg = 203 K. In the ND experiments, all samples exhibit three peaks corresponding to the correlations mentioned above. The widths of the interlayer peak at ca. 0.2 Å-1 changed drastically at the L-LC transitions, while the interionic peaks at ca. 1 Å-1 exhibited a small jump at Tc. The peak position and area of the three peaks did not change much at the transition. The structural changes were minimal at Tg. The QENS experiments demonstrated that the relaxation time of the interlayer motion increased tenfold at Tc, while those of other motions were monotonous in the whole temperature region. The structural and dynamical changes mentioned above are characteristic of the L-LC transition in imidazolium-based ionic liquids.

A Novel Bioabsorbable Sheet That Delivers NF-κB Decoy Oligonucleotide Restrains Abdominal Aortic Aneurysm Development in Rats.

For the suppression of inflammation in the aneurysm development, we focused on inhibition of an important transcription factor, nuclear factor-kappa B (NF-κB), using a decoy strategy. We newly developed a novel bioabsorbable sheet that delivers NF-κB decoy oligodeoxynucleotide (ODN).We treated 5-week-old SD rats that were induced with abdominal aortic aneurysm (AAA) using 0.5 M CaCl2 with an NF-κB decoy sheet. Four weeks after AAA induction, aortic tissue was excised for further examinations. We showed that this bioabsorbable sheet could deliver the decoy ODN into the target tissues and dissolve within a week. Treatment with the NF-κB decoy sheet reduced the aneurysm size compared with the controls. It also suppressed inflammation due to the effect of NF-κB decoy ODN. Immunohistochemistry revealed that the expression of CD31, CD4, and CD11b in the NF-κB decoy sheet group was significantly lower than in the control sheet group. The NF-κB decoy sheet was absorbed on the target tissue.We have revealed that the bioabsorbable sheet mediated decoy ODN is effective for transfection into target organs. We have also indicated that NF-κB decoy ODN transfection using this sheet has the potential to suppress the dilatation of aneurysm. The bioabsorbable sheet mediated transfection of the decoy ODN can be beneficial for the clinical treatment of AAA and other NF-κB-related cardiovascular diseases.

Increased Oral Porphyromonas gingivalis Prevalence in Cardiovascular Patients with Uncontrolled Diabetes Mellitus.

The aim of this study was to determine the correlation between periodontopathic bacteria and diabetes mellitus (DM) status in cardiovascular disease (CVD) subjects.DM is associated with the progression of periodontitis. Several epidemiological studies have suggested that periodontitis may be a risk factor for CVD. However, no study has compared the periodontal condition between well-controlled and poorly-controlled DM patients with CVD.The subjects were well-controlled (n = 73) or poorly-controlled (n = 39) DM patients with CVD. Blood examinations and dental clinical measurements, including number of teeth, probing pocket depth, bleeding on probing (BOP), and clinical attachment level (CAL) were performed. Periodontopathic bacterial existence was evaluated.Worsened CAL and BOP rate were detected in the uncontrolled DM group compared to the controlled group. We found increased salivary Porphyromonas gingivalis counts in the uncontrolled DM group compared to well-controlled DM subjects.Specific periodontopathic bacterial infection may affect DM condition in CVD patients.

Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome.

BACKGROUND: Marfan syndrome can cause life-threatening aortic complications. We investigated the relationship between FBN1 genotype and severe aortopathy (aortic root replacement, type A dissections, and related death). METHODS: We evaluated 248 patients with pathogenic or likely pathogenic FBN1 variants. The variants were classified as haploinsufficient type (HI, n=93) or dominant-negative type (DN, n=155) based on their location and predicted amino acid alterations, and we examined the effects of the FBN1 genotype on severe aortic events (aortic root replacement, type A dissections, and related death). RESULTS: The cumulative event-free probability was significantly lower in the HI group than in the DN group (adjusted hazard ratio, 2.1; 95% confidence interval, 1.4 -3.2; P<0.001). CONCLUSIONS: DN-CD+HI patients should be monitored more carefully than DN-nonCD patients for rapid development of aortic root aneurysms.

Specific periodontopathic bacterial infection affects hypertension in male cardiovascular disease patients.

Hypertension (HT) is a systemic disorder that results in the decline of quality of life and death. While patients with periodontitis are at a high risk of HT, little causal information has been provided to date. To clarify the relationship, periodontopathic bacterial infection in cardiovascular patients with or without HT was evaluated. The subjects were patients with (n = 412) or without (n = 199) HT who attended Tokyo Medical and Dental University hospital. Blood examinations and periodontal measurements were performed. Three periodontopathic bacteria existence and antibody titers were evaluated. We found that specific periodontopathic bacteria, Aggregatibacter actinomycetemcomitans and Prevotella intermedia, were highly detected in male subjects with HT compared to non-HT subjects, while they were comparable in the female patients. Mean probing pocket depth of elderly male patients with HT was higher compared to non-HT patients. The rates of obesity, dyslipidemia, and diabetes showed partial statistical difference between the two groups. Specific periodontopathic bacterial infection may affect HT in male cardiovascular patients.

Myocardial perfusion reserve quantified by cardiac magnetic resonance imaging is associated with late gadolinium enhancement in hypertrophic cardiomyopathy.

Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging has demonstrated the capability of stratifying hypertrophic cardiomyopathy (HCM). Stress perfusion test of CMR can quantify myocardial perfusion reserve (MPR), but its clinical role is not determined. The purpose of this study was to investigate the relationship between MPR and LGE in patients with HCM. A total of 61 consecutive cases underwent complete evaluation with electrocardiography and CMR [cine imaging, coronary MR angiography (MRA), and stress perfusion testing with LGE]. HCM cases were diagnosed by the Japanese conventional guideline prior to this CMR study. Mild LVH was defined as more than 13 mm in maximum LV wall thickness at end diastole on the cine imaging of the CMR. MPR was calculated as the ratio of stress/rest myocardial blood flow using an intensity curve on the stress perfusion test. Cases with ischemic heart disease were excluded from the study based on clinical history and coronary MRA. There were 37 HCM and 24 mild LVH cases (average age: 60.5 ± 10.9 vs. 64.8 ± 10.8; male: 62.2 vs. 75.0%, respectively, non-significant). MPR in HCM was lower than in LVH (1.5 ± 0.5 vs. 2.2 ± 0.9, p < 0.001) and normal subjects (2.4 ± 0.9, p < 0.001). MPR in HCM with LGE (N = 34) was lower than in HCM without LGE (N = 3) (1.4 ± 0.5 vs. 2.1 ± 0.2, p = 0.014). Multiple regression analysis verified that LGE was the strongest predictor of MPR among multiple clinical parameters, including LVH, LV dysfunction (ejection fraction < 50%), and the presence of negative T wave (p < 0.001). MPR was impaired in HCM with LGE compared with HCM without LGE. The clinical role of MPR on CMR needs to be clarified by further research.

The chemokine receptor type 4 antagonist, AMD3100, interrupts experimental tooth movement in rats.

OBJECTIVE: The aim of this study was to clarify the role of the stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis in osteoclast accumulation, and the influence of orthodontic tooth movement (OTM) under mechanical force application to periodontal tissues, by administration of the CXCR4 antagonist AMD3100. DESIGN: The upper right first molar (M1) of rats was moved mesially with a 10-g force titanium-nickel closed coil spring. Rats were treated with phosphate-buffered saline or AMD3100 (5mg/kg), which is a SDF-1 antagonist. After 0, 1, 3, and 7days, alveolar bones in all groups were examined at each time point by micro-computed tomography and histological analysis. RESULTS: Tooth movement was decreased significantly in the AMD3100-treated group at 1, 3, and 7days after beginning OTM. The numbers of tartrate-resistant acid phosphatase-positive multinucleated cells in the periodontal ligament around the maxillary M1 were decreased significantly in the treated as compared to the control group on Days 1 and 3. CONCLUSION: Administration of AMD3100 decreases OTM and osteoclast accumulation in rat molars under orthodontic force application. These findings suggest that the SDF-1/CXCR4 axis plays an important role in alveolar bone metabolism during OTM.

Japanese Cardiovascular Disease Patients with Diabetes Mellitus Suffer Increased Tooth Loss in Comparison to Those without Diabetes Mellitus -A Cross-sectional Study.

Objective Tooth loss is an irreversible condition that reflects the end-stage of oral diseases, including periodontitis. Although periodontitis is a major factor in the progression of diabetes mellitus (DM) and cardiovascular disease (CVD), no previous studies have compared tooth loss in CVD patients with and without DM. Methods The subjects included CVD patients with (n=94) and without (n=145) DM who attended Tokyo Medical and Dental University Hospital. Blood examinations and periodontal measurements were performed. Results The oral and periodontal examinations revealed that the numbers of missing teeth in the DM group were increased in comparison to the non-DM group. There was no significant difference between the groups with regard to the incidence of edentulism, the probing pocket depth, the clinical attachment level or the incidence of bleeding on probing. Conclusion We showed that the numbers of missing teeth among CVD patients with DM was significantly higher than that among CVD patients without DM.

Ultrasound microbubble-mediated transfection of NF-κB decoy oligodeoxynucleotide into gingival tissues inhibits periodontitis in rats in vivo.

Periodontitis is a chronic infectious disease for which the fundamental treatment is to reduce the load of subgingival pathogenic bacteria by debridement. However, previous investigators attempted to implement a nuclear factor kappa B (NF-κB) decoy oligodeoxynucleotide (ODN) as a suppressor of periodontitis progression. Although we recently reported the effectiveness of the ultrasound-microbubble method as a tool for transfecting the NF-κB decoy ODN into healthy rodent gingival tissue, this technique has not yet been applied to the pathological gingiva of periodontitis animal models. Therefore, the aim of this study was to investigate the effectiveness of the technique in transfecting the NF-κB decoy ODN into rats with ligature-induced periodontitis. Micro computed tomography (micro-CT) analysis demonstrated a significant reduction in alveolar bone loss following treatment with the NF-κB decoy ODN in the experimental group. RT-PCR showed that NF-κB decoy ODN treatment resulted in significantly reduced expression of inflammatory cytokine transcripts within rat gingival tissues. Thus, we established a transcutaneous transfection model of NF-κB decoy ODN treatment of periodontal tissues using the ultrasound-microbubble technique. Our findings suggest that the NF-κB decoy ODN could be used as a significant suppressor of gingival inflammation and periodontal disease progression.

Detrimental effects of specific Periodontopathic bacterial infection on tachyarrhythmia compared to Bradyarrhythmia.

BACKGROUND: Tachyarrhythmia (TA) and bradyarrhythmia (BA) are cardiac rhythm disorders that result in the decline of quality of life. While patients with periodontitis are at a high risk of cardiovascular disease (CVD), little causal information between TA and BA has been provided to date. To assess the relationship, periodontal bacterial infection in patients with TA or BA was evaluated. METHODS: The subjects were patients with TA (n = 98) or BA (n = 40) who attended Tokyo Medical and Dental University hospital. Periodontal and blood examinations were performed. Periodontopathic bacterial existence in saliva was evaluated. RESULTS: We found that specific periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, were highly detected in saliva from TA patients compared to BA subjects. The rates of hypertension and dyslipidemia were comparable between the two groups. CONCLUSION: Specific periodontal bacterial infection might affect TA progression.

Porphyromonas Gingivalis Elevated High-Mobility Group Box 1 Levels After Myocardial Infarction in Mice.

High mobility group box 1 (HMGB1) is a nuclear protein released from necrotic cells, inducing inflammatory responses. Epidemiological studies suggested a possible association between periodontitis and cardiovascular diseases (CVDs). Due to tissue damage and necrosis of cardiac cells following myocardial infarction (MI), HMGB1 is released, activating an inflammatory reaction. However, it remains unclear whether periodontitis is also involved in myocardial damage. The purpose of this study was to determine the effect of the periodontal pathogen Porphyromonas gingivalis (P.g.) after MI in mice.C57BL/6J wild type mice in post-MI were inoculated with P.g. in the infected group (P.g.-inoculated MI group) and with phosphate buffer saline (PBS) in the control group (PBS-injected MI group). Plasma samples and twelve tissue samples from mice hearts after MI were obtained. We determined the expression of HMGB1 by ELISA and immunohistochemistry.The level of HMGB1 protein in the P.g.-inoculated MI group was significantly higher than in the PBS-injected MI group on day 5, but not on day 14. Immunohistochemistry analysis revealed that HMGB1 was mainly expressed in cardiomyocytes, immune cells, and vascular endothelial cells in the PBS-injected MI group, while HMGB1 was seen broadly in degenerated cardiomyocytes, extracellular fields, immune cells, and vascular endothelial cells in the P.g.-inoculated MI group. A significant increase in the number of HMGB1 positive cells was observed in the P.g.-inoculated MI group compared to the PBS-injected MI group.Infection with P.g. after MI enhanced myocardial HMGB1 expression. There is a possible relationship between periodontitis and post-infarction myocardial inflammation through HMGB-1.

Novel Concept of a Heart-Gut Axis in the Pathophysiology of Heart Failure.

Patients with heart failure (HF) have structural and functional changes of the gut as a result of microcirculatory disturbances. A disrupted gut epithelial barrier may lead to translocation of microbial products into systemic circulation, possibly aggravating HF by inducing inflammatory responses. Gut microbiota play an essential role in the maintenance of host homeostasis because large quantities of their gene products complement host physiological processes. Emerging evidence has suggested the potential clinical significance of gut microbiota in the pathophysiology of HF. Imbalances of gut microbe-derived metabolites can contribute to cardiac dysfunction and other morbidities in patients with HF. Therapeutic research for HF through targeting microbiota is under way. Thus, the novel concept of a heart-gut axis may lead to breakthroughs in the development of innovative diagnostics and therapeutic approaches for HF.