Microbiome Analysis Research Articles

Microbiome and network analysis reveal potential mechanisms underlying Carassius auratus diseases: The interactions between critical environmental and microbial factors

Despite the rapid development of research on aquatic environment microbiota, limited attention has been paid to exploring the complex interactions between microbial communities and aquatic environments. Particularly, the mechanisms underlying fish diseases based on such dynamic interactions remain unknown. This study aimed to address the gap by conducting microbiome and co-occurrence network analyses on the typical freshwater aquaculture systems. High-throughput 16S rRNA gene sequencing results revealed significant differences in the microbiota between the disease and healthy groups. Notably, disease mortality varied consistently with the gradient of relative abundance of Proteobacteria (intestine, R2 = 0.46, p < 0.05) and Cyanobacteria (gill, R2 = 0.67, p < 0.01), indicating their potential use as diagnostic criteria. Furthermore, the elevated hepatosomatic index, NO3-N, COD and TC (sediment) were directly correlated with diseases (r > 0.54, p < 0.01). Mean concentrations of NO3-N, COD and TC were elevated by 78.87%, 25.63% and 44.2%, respectively, in ponds where diseases occurred. Quantitative analysis (qPCR) revealed that Aeromonas sobria infected hosts through a potential pathway of “sediment (4.4 × 105 copy number/g)-water (1.1 × 103 copy number/mL)-intestine (1.2 × 106 copy number/g)”. Similarly, the potential route for Aeromonas veronii was sediment (4.9 × 106 copy number/g) to gill (5.1 × 105 copy number/g). Additionally, the complexity of microbial networks in the intestine, water, and sediment was significantly lower in the disease group, although no similar phenomenon was observed in the gill microbial network. In summary, these findings reveal that elevated concentrations of crucial environmental factors disrupt the linkages within microbiota, fostering the growth of opportunistic bacteria capable of colonizing fish gut or gills. This offers new insights into potential mechanisms by which environmental factors cause disease in fish.

Bacillus suppresses nitrogen efficiency of soybean-rhizobium symbiosis through regulation of nitrogen-related transcriptional and microbial patterns.

The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.

Integrated Analysis of Gut microbiome, Inflammation and Neuroimaging Features Supports the Role of Microbiome-Gut-Brain Crosstalk in Schizophrenia

Abstract Background and Hypothesis Gut microbiota has been implicated in the pathogenesis of schizophrenia (SZ) and relevant changes in the brain, but the underlying mechanism remains elusive. This study aims to investigate the microbiota-gut-brain crosstalk centered on peripheral inflammation in SZ patients. Study Design We recruited a cohort of 182 SZ patients and 120 healthy controls (HC). Multi-omics data, including fecal 16S rRNA, cytokine data, and neuroimaging data, were collected and synthesized for analysis. Multi-omics correlations and mediation analyses were utilized to determine the associations of gut microbiome with inflammatory cytokines and neuroimaging characteristics. Additionally, machine learning models for effective SZ diagnosis were separately generated based on gut microbial and neuroimaging data. Study Results Gut microbial dysbiosis, characterized by a decrease in butyrate-producing bacteria and an increase in pro-inflammatory bacteria, has been identified in SZ patients. These key microbial taxa were associated with increased inflammatory cytokines, potentially through mediating lipid metabolic pathways such as steroid biosynthesis and linoleic acid metabolism. Further analysis revealed altered microbial genera to be correlated with disrupted gray matter volume and regional homogeneity in SZ patients. Importantly, certain inflammatory cytokines mediated the relationship between the SZ-enriched genus Succinivibrio and aberrant activity of anterior cingulate cortex and left inferior temporal gyrus in the SZ group. Moreover, the classification model based on gut microbial data showed comparable efficacy to the model based on brain functional signatures in SZ diagnosis. Conclusions This study presents evidence for the dysregulated microbiota-gut-brain axis in SZ and emphasizes the central role of peripheral inflammation.

Metabolome and microbiome analyses reveal the efficacy of Shen-Fu formula in treating heart failure.

Improvement of strategies to treat heart failure (HF) has been a longstanding global goal and challenge. Shen-Fu formula (SF), as a classic herbal preparation, has demonstrated efficacy in treating HF in clinical settings. However, further understanding of the therapeutic mechanisms of SF is required. In this study, metabolomics and 16S rDNA sequencing were used to analyze the effects of SF on metabolic profiling and gut microbiota in HF rats. After 4 weeks of SF treatment, the cardiac function of HF rats showed improvement, with a significant increase in ejection fraction and fractional shortening, as well as a significant decrease in left ventricular volume and mass. Metabolomics study revealed that SF regulates the levels of substances related to energy metabolism, primarily involving lysophosphatidylcholines and polyunsaturated fatty acids. In addition, we found that SF regulates the structure of the microbial community in HF rats and modulates the balance between probiotic and pathogenic bacteria. Furthermore, the SF combination exhibited a superior effect that was better than the use of each herb separately. These results demonstrate the potential of SF therapy in the management of HF and highlight the role of SF in regulating fatty acid metabolism and gut microbiome during HF.

Fluconazole worsened lung inflammation, partly through lung microbiome dysbiosis in mice with ovalbumin-induced asthma

Innate immunity in asthma may be influenced by alterations in lung microbiota, potentially affecting disease severity. This study investigates the differences in lung inflammation and microbiome between asthma-ovalbumin (OVA) administered with and without fluconazole treatment in C57BL/6 mice. Additionally, the role of inflammation was examined in an in vitro study using a pulmonary cell line. At 30 days post-OVA administration, allergic asthma mice exhibited increased levels of IgE and IL-4 in serum and lung tissue, higher pathological scores, and elevated eosinophils in bronchoalveolar lavage fluid (BALF) compared to control mice. Asthma inflammation was characterized by elevated serum IL-6, increased lung cytokines (TNF-α, IL-6, IL-10), and higher fungal abundance confirmed by polymerase chain reaction (PCR). Fluconazole-treated asthma mice displayed higher levels of cytokines in serum and lung tissue (TNF-α and IL-6), increased pathological scores, and a higher number of mononuclear cells in BALF, with undetectable fungal levels compared to untreated mice. Lung microbiome analysis revealed similarities between control and asthma mice; however, fluconazole-treated asthma mice exhibited higher Bacteroidota levels, lower Firmicutes, and reduced bacterial abundance. Pro-inflammatory cytokine production was increased in supernatants of the pulmonary cell line (NCI-H292) after co-stimulation with LPS and beta-glucan (BG) compared to LPS alone. Fluconazole treatment in OVA-induced asthma mice exacerbated inflammation, partially due to fungi and Gram-negative bacteria, as demonstrated by LPS+BG-activated pulmonary cells. Therefore, fluconazole should be reserved for treating fungal asthma rather than asthma caused by other etiologies.

Alterations of gut microbiome profiles as potential markers in patients developing acute coronary syndrome

Abstract Background Imbalanced gut microbiota or gut dysbiosis leads to systemic inflammation, one of key contributors to the development and progression of atherosclerosis. A recent study revealed the association of the gut microbiota and the severity of coronary artery lesions in patients with acute coronary syndrome (ACS). However, the gut microbiota profile in ACS patients in comparison with patients with high-risk cardiovascular disease (CVD) has not been thoroughly investigated. Purpose We aimed to compare the profiles of gut microbiome between patients with ACS and patients with high-risk CVD, as well as to determine the association between gut microbiota and CVD risk factors. Methods This cross-sectional study enrolled 24 stabilized ACS patients within 24 hrs of hospitalization and 59 outpatients in CVD clinics, as a control group. Echocardiography was done in those patients. Blood was collected for biochemical analysis, and fecal samples were collected for gut microbiome analysis via 16S RNA sequencing. Results The demographic data showed no significant differences between groups in CVD risk factors (age, levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides). However, patients with ACS had greater cigarette use and alcohol consumption than the control group. For gut microbiome, both alpha and beta diversity levels of ACS group were significantly higher than those in a control group (Figure 1A-B). Differential abundance analysis by ANCOM-BC revealed significantly increased level of bacteria in the Atopobiaceae family in ACS patients, compared to controls (Figure 1C). Since Atopobiaceae was reported to be positively associated with percent atheroma volume (PAV), a marker of plaque deposit in the arteries, we found an increased number of Atopobiaceae which was positively associated with serum Troponin T level (Figure 1D), systemic inflammation (Figure 1E), and a trend to negatively correlated with LV ejection fraction. Conclusion Our findings suggested that alterations of gut microbiota occurred in ACS patients, and an increase in gut Atopobiaceae level could potentially be the predictive marker of the development of ACS in CVD patients.Figure 1

Unveiling the Gut Microbiome of Malaysia's Colobine Monkeys : Insights into Health and Evolution.

Colobines are primarily leaf-eating primates, depend on microbiota of gastrointestinal tracts for food digestion. However, the gut microbiota of Malaysia's colobines specifically langurs remains unstudied. Hence, we aim to analyze the fecal microbiomes of Malaysia's langurs using Presbytis femoralis, Presbytis robinsoni, Trachypithecus obscurus, and Trachypithecus cristatus from various landscapes as models. We collected samples from all four species across several areas in Peninsular Malaysia and performed 16S ribosomal RNA gene amplicon sequencing using the Illumina sequencing platform. Presbytis femoralis exhibited the highest bacterial diversity, followed by T. obscurus, T. cristatus, P. robinsoni and the lowest, P. siamensis. Over 11 million operational taxonomic units (OTUs) were identified across Malaysia's langurs spanning 26 phyla, 180 families, and 329 genera of microbes. The OTUs were dominated by Firmicutes, Proteobacteria, and Bacteroidetes. There are 11 genera of pathogenic bacteria were identified across all host species. Nine pathogenic bacterial genera inhabit both T. obscurus, indicating poor health due to low bacterial diversity and heightened pathogenicity. In contrast, P. robinsoni with the fewest pathogenic species is deemed the healthiest among Malaysia's langurs. This study demonstrates that alterations in diet, behavior, and habitat affect bacterial diversity in Malaysia's langurs' gut microbiota. Even though this is the first comprehensive analysis of langur microbiomes in Malaysia, it is important to note the limitations regarding the number of samples, populations sampled, and the geographical origins and landscapes of these populations. Our results suggest that Malaysia's langurs may harbor pathogenic bacteria, potentially posing a risk of transmission to humans. This highlights the critical need for the conservation and management of Malaysia's langurs, particularly considering their interactions with humans. This data can serve as a foundation for authorities to inform the public about the origins and significance of animal health and the management of zoonotic diseases.

FMT and TCM to treat diarrhoeal irritable bowel syndrome with induced spleen deficiency syndrome- microbiomic and metabolomic insights

BackgroundDiarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites.MethodsThe new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model ( 3 groups) rats were prepared articially using mother’s separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database.ResultsSignificant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P < 0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles.ConclusionFMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome.

Time-restricted feeding mediated modulation of microbiota leads to changes in muscle physiology in Drosophila obesity models.

Recent research has highlighted the essential role of the microbiome in maintaining skeletal muscle physiology. The microbiota influences muscle health by regulating lipid metabolism, protein synthesis, and insulin sensitivity. However, metabolic disturbances such as obesity can lead to dysbiosis, impairing muscle function. Time-restricted feeding (TRF) has been shown to mitigate obesity-related muscle dysfunction, but its effects on restoring healthy microbiomes remain poorly understood. This study utilizes 16S microbiome analysis and bacterial supplementation to investigate the bacterial communities influenced by TRF that may benefit skeletal muscle physiology. In wild-type and obese Drosophila models (axenic models devoid of natural microbial communities), the absence of microbiota influence muscle performance and metabolism differently. Specifically, axenic wild-type Drosophila exhibited reduced muscle performance, higher glucose levels, insulin resistance, ectopic lipid accumulation, and decreased ATP levels. Interestingly, in obese Drosophila (induced by a high-fat diet or predisposed obesity mutant Sk2), the absence of microbiota improved muscle performance, lowered glucose levels, reduced insulin resistance, and increased ATP levels. TRF was found to modulate microbiota composition, notably increasing Acetobacter pasteurianus (AP) and decreasing Staphylococcus aureus (SA) in both obesity models. Supplementation with AP improved muscle performance and reduced glucose and insulin resistance, while SA supplementation had the opposite effect. This study provides novel insights into the complex interactions between TRF, microbiota, and skeletal muscle physiology in different Drosophila models.

Taeniasis impacts human gut microbiome composition and function.

Human taeniasis, caused by Taenia tapeworms, is a global parasitic disease with significant implications for public health and food safety. These tapeworms can grow to considerable sizes and potentially impact the microecology of the host gut. Despite their importance, the effects of Taenia infection on host gut microbiota haven't been thoroughly investigated. In this study, we conducted a cross-sectional analysis of the gut microbiome in patients infected with Taenia asiatica (n = 87) compared to healthy controls (n = 79) in the Dali cohort, China. We also performed a longitudinal assessment of microbial changes following deworming in a subset of patients (n = 24). Our findings reveal a significant shift in gut microbial composition, characterized by increased alpha-diversity and an enrichment of Prevotella-driven enterotypes in infected patients compared to healthy controls. The stability of these microbial features post-deworming varied widely among individuals and was lower in those with lower initial alpha diversity and Prevotella-enterotype before deworming. We observed a significant depletion of Bifidobacterium species in infected individuals, regardless of enterotypes, and these prebiotics did not recover post-deworming. Metabolic network analysis and in vitro experiments suggest that the reduction of Bifidobacterium was linked to metabolic competition for ecological niches or nutrients, particularly stachyose, from other microbes rather than the parasitism itself. Furthermore, our machine learning analysis demonstrated that taxa associated with Bifidobacterium in stachyose metabolism could robustly predict infection but could not predict deworming. This study highlights the substantial impact of taeniasis on the human gut microbiome and overall gut health.

The potential of including the microbiome as biomarker in population-based health studies: methods and benefits

The key role of our microbiome in influencing our health status, and its relationship with our environment and lifestyle or health behaviors, have been shown in the last decades. Therefore, the human microbiome has the potential to act as a biomarker or indicator of health or exposure to health risks in the general population, if information on the microbiome can be collected in population-based health surveys or cohorts. It could then be associated with epidemiological participant data such as demographic, clinical or exposure profiles. However, to our knowledge, microbiome sampling has not yet been included as biological evidence of health or exposure to health risks in large population-based studies representative of the general population. In this mini-review, we first highlight some practical considerations for microbiome sampling and analysis that need to be considered in the context of a population study. We then present some examples of topics where the microbiome could be included as biological evidence in population-based health studies for the benefit of public health, and how this could be developed in the future. In doing so, we aim to highlight the benefits of having microbiome data available at the level of the general population, combined with epidemiological data from health surveys, and hence how microbiological data could be used in the future to assess human health. We also stress the challenges that remain to be overcome to allow the use of this microbiome data in order to improve proactive public health policies.

Alterations in purine and pyrimidine metabolism associated with latent tuberculosis infection: insights from gut microbiome and metabolomics analyses.

Individuals with latent tuberculosis infection (LTBI) account for almost 30% of the population worldwide and have the potential to develop active tuberculosis (ATB). Despite this, the current understanding of the pathogenesis of LTBI is limited. The gut microbiome can be altered in tuberculosis patients, and an understanding of the changes associated with the progression from good health to LTBI to ATB can provide novel perspectives for understanding the pathogenesis of LTBI by identifying microbial and molecular biomarkers associated therewith. In this study, fecal samples from healthy controls (HC), individuals with LTBI and ATB patients were collected for gut microbiome and metabolomics analyses. Compared to HC and LTBI subjects, participants with ATB showed a significant decrease in gut bacterial α-diversity. Additionally, there were significant differences in gut microbial communities and metabolism among the HC, LTBI, and ATB groups. PICRUSt2 analysis revealed that microbiota metabolic pathways involving the degradation of purine and pyrimidine metabolites were upregulated in LTBI and ATB individuals relative to HCs. Metabolomic profiling similarly revealed that purine and pyrimidine metabolite levels were decreased in LTBI and ATB samples relative to those from HCs. Further correlation analyses revealed that the levels of purine and pyrimidine metabolites were negatively correlated with those of gut microbial genera represented by Ruminococcus_gnavus_group (R. gnavus), and the levels of R. gnavus were also positively correlated with adenosine nucleotide degradation II, which is a purine degradation pathway. Moreover, a combined signature including hypoxanthine and xanthine was found to effectively distinguish between LTBI and HC samples (area under the curve [AUC] of training set = 0.796; AUC of testing set = 0.924). Therefore, through gut microbiome and metabolomic analyses, these findings provide valuable clues regarding how alterations in gut purine and pyrimidine metabolism are linked to the pathogenesis of LTBI.IMPORTANCEThis study provides valuable insight into alterations in the gut microbiome and metabolomic profiles in a cohort of adults with LTBI and ATB. Perturbed gut purine and pyrimidine metabolism in LTBI was associated with the compositional alterations of gut microbiota, which may be an impetus for developing novel diagnostic strategies and interventions targeting LTBI.

Development and evaluation of a web-based diet quality screener for vegans (VEGANScreener): a cross-sectional, observational, multicenter, clinical study

Consumption of plant-based diets, including vegan diets, necessitates attention to the quality of the diet for the prevention and early detection of nutritional deficiencies. Within the VEGANScreener project, a unique brief screening tool for the assessment and monitoring of diet quality among vegans in Europe was developed. To provide a standardized tool for public use, a clinical study will be conducted to evaluate the VEGANScreener against a reference dietary assessment method and nutritional biomarkers. An observational study is set to include 600 participants across five European sites – Belgium, Czech Republic, Germany, Spain, and Switzerland. In total, 400 self-reported vegans (≥2 years on a vegan diet), and 170 self-reported omnivore controls will be examined, aged between 18 and 65 years, with males and females being equally represented in a 1:1 ratio for two age groups (18–35 and 36–65 years). Participants with diseases affecting metabolism and intestinal integrity will be excluded. The clinical assessment will include a structured medical history, along with taking blood pressure and anthropometric measurements. Blood and urine will be sampled and analyzed for a set of dietary biomarkers. Metabolomic analyses will be conducted to explore potential novel biomarkers of vegan diet. Moreover, saliva samples will be collected to assess the metabolome and the microbiome. Participants will receive instructions to complete a nonconsecutive 4-day diet record, along with the VEGANScreener, a socio-demographic survey, a well-being survey, and a FFQ. To evaluate reproducibility, the VEGANScreener will be administered twice over a three-weeks period. Among vegans, the construct validity and criterion validity of the VEGANScreener will be analyzed through associations of the score with nutrient and food group intakes, diet quality scores assessed from the 4-day diet records, and associations with the dietary biomarkers. Secondary outcomes will include analysis of dietary data, metabolomics, and microbiomes in all participants. Major nutrient sources and variations will be assessed in the sample. Exploratory metabolomic analysis will be performed using multivariable statistics and regression analysis to identify novel biomarkers. Standard statistical models will be implemented for cross-sectional comparisons of geographical groups and vegans versus omnivores.

Optimal 16S rRNA gene amplicon sequencing analysis for oral microbiota to avoid the potential bias introduced by trimming length, primer, and database.

16S rRNA gene amplicon sequencing analysis is used to investigate bacterial communities; however, the estimated bacterial composition can differ from the original due to experimental and analytical biases. Therefore, this study determines the optimal conditions to minimize the potential biases in 16S rRNA gene amplicon sequencing analysis using different DNA samples, trimming lengths, primers, and databases. The results of the mock1 community with 250 and 300 bp paired-end (PE), comprising 15 bacteria from various environments, showed the highest similarity between the theoretical value and the data using the Greengenes2 and the V3 region at the genus level and V5-V6 at the species level. In the 300 bp PE sequencing analysis of the mock2 community, comprising six major oral bacteria, the data using the V3-V4, V4, and V5-V6 regions with the SILVA, Greengenes2, and the Human Oral Microbiome Database (HOMD) showed the highest similarity to the theoretical values at the genus level. At the species level, the data using the V3-V4 and V4 regions with Greengenes2 and the data using the V1-V2 with HOMD exhibited the highest alignment with the theoretical values. In the species analysis of the dental calculus samples with 300 bp PE, the Shannon index value was higher with the V1-V2 region and HOMD than with others. Our results suggest that the optimal conditions for oral microbiome analysis are the combinations of 300 bp PE and the V3-V4 or V4 region with the Greengenes2 and the V1-V2 with HOMD.IMPORTANCEThe 16S rRNA gene amplicon sequencing analysis is frequently used in oral microbiome research. However, this method can have biases that distort the experimental data, which depend on the methodological steps, including sequencing length, trimming length, selected amplification regions, and referenced databases. In this study, a combination of 300 bp PE and the primer targeting the V3-V4 or V4 regions with the Greengenes2 and the V1-V2 region with the HOMD was the most bias-minimizing condition for oral microbiota analysis. In addition, this is the first report of such analyses in modern Japanese dental calculus. The methods used in this study will aid in setting appropriate conditions for sequence analysis of microbiota obtained not only from the oral cavity but also from any environment.

Integrated analysis of metabolome and microbiome in a rat model of perimenopausal syndrome.

In this work, we employed 16S ribosomal RNA gene sequencing to analyze the gut microbes in stool samples. In addition, we conducted an ultra-high-performance liquid chromatography-tandem mass spectrometry-based metabolomics approach on gut tissue and serum obtained from rats with perimenopausal syndrome (PMS) and healthy controls. By characterizing the composition and metabolomic properties of gut microbes in PMS rats, we aim to enhance our understanding of their role in women's health, emphasizing the significance of regulating gut microbes in the context of menopausal women's well-being. We aim to provide a theoretical basis for the prevention and treatment of PMS in terms of gut microflora as well as metabolism.

Microbial metabolomics in acute myeloid leukemia: From pathogenesis to treatment.

Acute myeloid leukemia (AML), the most common leukemia in adults, is a biologically heterogeneous disease arising from clonally proliferating hematopoietic stem cells. Increased appreciation of novel genetic methods has improved the understanding of AML biology. Recently, the emerging field of metabolomics has indicated qualitative and quantitative alterations in metabolic profiles in AML pathogenesis, progression and treatment. Multiple metabolic and molecular pathways regulate human metabolism and host-microbiome interactions may significantly affect this biochemical machinery. Microbiota have been found to play a significant role in hematopoietic function, metabolism and immunity, contributing to AML occurrence. A large number of studies have highlighted the importance of the composition and diversity of the gut microbiota (GM) in response to treatment and prognosis in AML. Moreover, strong evidence emphasizes the detrimental link between dysbiosis and infectious complications, a leading cause of morbidity and mortality for patients with AML. Several microbiota-related mechanisms have been linked to particular changes in host physiology so far, and microbial-derived metabolites belong to one of the most important. Circulating in the body, they modulate human conditions both locally and systemically. The extensive and diverse repertoire of bacterial metabolic functions plays a critical role in numerous processes, including leukemogenesis. Integrative analysis of microbiome and metabolome data is a promising avenue for better understanding the complex relationship between the microbiota, biochemical alterations and AML pathogenesis to effectively prevent, treat and mitigate its outcomes. This review concentrates on the pathologic roles and therapeutic implications of microbe-derived metabolites in AML settings.

Aging-induced dysbiosis worsens sepsis severity but is attenuated by probiotics in D-galactose-administered mice with cecal ligation and puncture model.

Despite the well-established effects of aging on brain function and gut dysbiosis (an imbalance in gut microbiota), the influence of aging on sepsis-associated encephalopathy (SAE) and the role of probiotics in this context remain less understood. C57BL/6J mice (8-week-old) were subcutaneously administered with 8 weeks of D-galactose (D-gal) or phosphate buffer solution (PBS) for aging and non-aging models, respectively, with or without 8 weeks of oral Lacticaseibacillus rhamnosus GG (LGG). Additionally, the impact of the condition media from LGG (LCM) was tested in macrophages (RAW 264.7 cells), microglia (BV-2 cells), and hippocampal cells (HT-22 cells). Fecal microbiome analysis demonstrated D-gal-induced dysbiosis (reduced Firmicutes and Desulfobacterota with increased Bacteroidota and Verrucomicrobiota), which LGG partially neutralized the dysbiosis. D-gal also worsens cecal ligation and puncture (CLP) sepsis severity when compared with PBS-CLP mice, as indicated by serum creatinine (Scr) and alanine transaminase (ALT), but not mortality, neurological characteristics (SHIRPA score), and serum cytokines (TNF-α and IL-6). Additionally, D-gal-induced aging was supported by fibrosis in the liver, kidney, and lung; however, CLP sepsis did not worsen fibrosis. Interestingly, LGG attenuated all parameters (mortality, Scr, ALT, SHIRPA, and cytokines) in non-aging sepsis (PBS-CLP) while improving all these parameters, except for mortality and serum IL-6, in aging sepsis (D-gal CLP). For the in vitro test using lipopolysaccharide (LPS) stimulation, LCM attenuated inflammation in some parameters on RAW264.7 cells but not BV-2 and HT-22 cells, implying a direct anti-inflammatory effect of LGG on macrophages, but not in cells from the brain. D-gal induced fecal dysbiosis and worsened sepsis severity as determined by Scr and ALT, and LGG could alleviate most of the selected parameters of sepsis, including SAE. However, the impact of LGG on SAE was not a direct delivery of beneficial molecules from the gut to the brain but partly due to the attenuation of systemic inflammation through the modulation of macrophages.

Environmental Heat Stress Decreases Sperm Motility by Disrupting the Diurnal Rhythms of Rumen Microbes and Metabolites in Hu Rams.

Heat stress (HS) has become a common stressor, owing to the increasing frequency of extreme high-temperature weather triggered by global warming, which has seriously affected the reproductive capacity of important livestock such as sheep. However, little is known about whether HS reduces sperm motility by inducing circadian rhythm disorders in rumen microorganisms and metabolites in sheep. In this study, the year-round reproduction of two-year-old Hu rams was selected, and the samples were collected in May and July 2022 at average environmental temperatures between 18.71 °C and 33.58 °C, respectively. The experiment revealed that the mean temperature-humidity index was 86.34 in July, indicating that Hu rams suffered from HS. Our research revealed that HS significantly decreased sperm motility in Hu rams. Microbiome analysis further revealed that HS reshaped the composition and circadian rhythm of rumen microorganisms, leading to the circadian disruption of microorganisms that drive cortisol and testosterone synthesis. Serum indicators further confirmed that HS significantly increased the concentrations of cortisol during the daytime and decreased the testosterone concentration at the highest body temperature. Untargeted metabolomics analysis revealed that the circadian rhythm of rumen fluid metabolites in the HS group was enriched by the cortisol and steroid synthesis pathways. Moreover, HS downregulated metabolites, such as kaempferol and L-tryptophan in rumen fluid and seminal plasma, which are associated with promotion of spermatogenesis and sperm motility; furthermore, these metabolites were found to be strongly positively correlated with Veillonellaceae_UCG_001. Overall, this study revealed the relationship between the HS-induced circadian rhythm disruption of rumen microorganisms and metabolites and sperm motility decline. Our findings provide a new perspective for further interventions in enhancing sheep sperm motility with regard to the circadian time scale.

Insights into the Gut Microbial Diversity of Wild Siberian Musk Deer (Moschus moschiferus) in Republic of Korea.

The gut microbiota plays a crucial role in the health and well-being of wildlife. However, its composition and diversity remain unexplored, particularly in threatened species such as the Siberian musk deer (SMD). This study aimed to elucidate the gut microbiota composition within different wild SMD communities for assessing their health status. We conducted the first comprehensive fecal microbiome analysis of wild SMD inhabiting three distinct locations in Gangwon Province, Republic of Korea (Korea). Fecal samples were collected non-invasively and 16S rRNA gene sequencing was performed for gut microbiota characterization. Consistent with previous research, Firmicutes and Bacteroidetes were the dominant phyla in the gut microbiota of wild SMD. Planctomycetota was a prevalent phylum in wild SMD gut microbiota, warranting further investigation of its ecological significance. While significant differences were observed in the gut microbiota richness among the three groups, no significant disparities were detected in the beta diversity. Additionally, certain genera exhibited distinct relative abundances among the groups, suggesting potential associations with geographic factors, gut disorders, and dietary habits. Our findings provide valuable insights into the gut microbiome of wild SMD and offer a foundation for future microbiome-based conservation efforts for this vulnerable species.

Evaluation of the Human Placental Microbiota in Early- and Late-Onset Pre-Eclampsia.

Despite many decades of research, the exact etiology of pre-eclampsia (PE) remains unknown. Several etiopathologies have been suggested, including the role of the placental microbiota. However, the existence of placental microbiota and its possible contribution to pregnancy complications, particularly PE has remained controversial. The present study was designed to identify different microbes that co-exist the placenta of women with early- and late-onset PE. Thirty age-matched normotensive and early-onset as well as age-matched normotensive and late-onset pre-eclamptic women respectively, were recruited. After obtaining an informed consent, the placental tissues were obtained through caesarian section with sterile and standardized clinical procedures. DNA was extracted from each tissue and microbiome analysis was conducted using a targeted 16S analysis and the reads were analyzed with bioinformatics. There was a significance difference between the blood pressure of early-/late-onset PE compared with age-matched normotensive controls, respectively. In addition, the reads from placencental samples were classified as belonging to the phyla, Actinobacteria, Firmicutes, Bacteroidetes, Proteobacteria, with Proteobacteria dominated by the classes Pseudomonadales and Gammaproteobacteria with smaller amounts of Actinobacteria and Bacteroidetes. There was no significant difference between the placental bacterial species of early-/late-onset PE compared with age-matched normotensive controls, respectively. Further analysis found no correlation between bacterial species and early- or late-onset PE. The present results demonstrate a low biomass of bacterial species, which might further indicate that the placental samples had very low levels of bacteria species and there is no correlation between the bacterial composition and early- or late-onset PE.