Environmental, socioeconomic, and health factors associated with gut microbiome species and strains in isolated Honduras villages.

Despite a growing interest in the gut microbiome of non-industrialized countries, data linking deeply sequenced microbiomes from such settings to diverse host phenotypes and situational factors remain uncommon. Using metagenomic data from a community-based cohort of 1,871 people from 19 isolated villages in the Mesoamerican highlands of western Honduras, we report associations between bacterial species and human phenotypes and factors. Among them, socioeconomic factors account for 51.44% of the total associations. Meta-analysis of species-level profiles across several datasets identified several species associated with body mass index, consistent with previous findings. Furthermore, the inclusion of strain-phylogenetic information modifies the overall relationship between the gut microbiome and the phenotypes, especially for some factors like household wealth (e.g., wealthier individuals harbor different strains of Eubacterium rectale). Our analysis suggests a role that gut microbiome surveillance can play in understanding broad features of individual and public health.

The effect of successive summer drought periods on bacterial diversity along a plant species richness gradient.

Drought is a major stressor to soil microbial communities, and the intensification of climate change is predicted to increase hydric stress worldwide in the coming decades. As a possible mitigating factor for the consequences of prolonged drought periods, above and belowground biodiversity can increase ecosystem resistance and resilience by improving metabolic redundancy and complementarity as biodiversity increases. Here, we investigated the interaction effect between plant richness and successive, simulated summer drought on soil microbial communities during a period of 9 years.To do that, we made use of a well-established biodiversity experiment (The Jena Experiment) to investigate the response of microbial richness and community composition to successive drought periods alongside a plant richness gradient, which covers 1-, 2-, 4-, 8-, 16-, and 60-species plant communities. Plots were covered from natural precipitation by installing rain shelters 6 weeks every summer. Bulk soil samples were collected 1 year after the last summer drought was simulated. Our data indicate that bacterial richness increased after successive exposure to drought, with the increase being stable along the plant richness gradient. We identified a significant effect of plant species richness on the soil microbial community composition and determined the taxa significantly impacted by drought at each plant richness level. Our data successfully demonstrates that summer drought might have a legacy effect on soil bacterial communities.

Gut microbiota DPP4-like enzymes are increased in type-2 diabetes and contribute to incretin inactivation.

BACKGROUND: The gut microbiota controls broad aspects of human metabolism and feeding behavior, but the basis for this control remains largely unclear. Given the key role of human dipeptidyl peptidase 4 (DPP4) in host metabolism, we investigate whether microbiota DPP4-like counterparts perform the same function. RESULTS: We identify novel functional homologs of human DPP4 in several bacterial species inhabiting the human gut, and specific associations between Parabacteroides and Porphyromonas DPP4-like genes and type 2 diabetes (T2D). We also find that the DPP4-like enzyme from the gut symbiont Parabacteroides merdae mimics the proteolytic activity of the human enzyme on peptide YY, neuropeptide Y, gastric inhibitory polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) hormones in vitro. Importantly, administration of E. coli overexpressing the P. merdae DPP4-like enzyme to lipopolysaccharide-treated mice with impaired gut barrier function reduces active GIP and GLP-1 levels, which is attributed to increased DPP4 activity in the portal circulation and the cecal content. Finally, we observe that linagliptin, saxagliptin, sitagliptin, and vildagliptin, antidiabetic drugs with DPP4 inhibitory activity, differentially inhibit the activity of the DPP4-like enzyme from P. merdae. CONCLUSIONS: Our findings confirm that proteolytic enzymes produced by the gut microbiota are likely to contribute to the glucose metabolic dysfunction that underlies T2D by inactivating incretins, which might inspire the development of improved antidiabetic therapies.

Ex vivo metabolism kinetics of primary to secondary bile acids via a physiologically relevant human faecal microbiota model.

Bile acids (BA) are synthesized in the human liver and undergo metabolism by host gut bacteria. In diseased states, gut microbial dysbiosis may lead to high primary unconjugated BA concentrations and significant perturbations to secondary BA. Hence, it is important to understand the microbial-mediated formation kinetics of secondary bile acids using physiologically relevant ex vivo human faecal microbiota models. Here, we optimized an ex vivo human faecal microbiota model to recapitulate the metabolic kinetics of primary unconjugated BA and applied it to investigate the formation kinetics of novel secondary BA metabolites and their sequential pathways. We demonstrated (1) first-order depletion of primary BA, cholic acid (CA) and chenodeoxycholic acid (CDCA), under non-saturable conditions and (2) saturable Michaelis-Menten kinetics for secondary BA metabolite formation with increasing substrate concentration. Notably, relatively lower Michaelis constants (Km) were associated with the formation of deoxycholic acid (DCA, 14.3 µM) and lithocholic acid (LCA, 140 µM) versus 3-oxo CA (>1000 µM), 7-keto DCA (443 µM) and 7-keto LCA (>1000 µM), thereby recapitulating clinically observed saturation of 7α-dehydroxylation relative to oxidation of primary BA. Congruently, metagenomics revealed higher relative abundance of functional genes related to the oxidation pathway as compared to the 7α-dehydroxylation pathway. In addition, we demonstrated gut microbial-mediated hyocholic acid (HCA) and hyodeoxycholic acid (HDCA) formation from CDCA. In conclusion, we optimized a physiologically relevant ex vivo human faecal microbiota model to investigate gut microbial-mediated metabolism of primary BA and present a novel gut microbial-catalysed two-step pathway from CDCA to HCA and, subsequently, HDCA.

Compost-diatomite-based phytostabilization course under extreme environmental conditions in terms of high pollutant contents and low temperatures.

The effects of changes in environmental temperatures on the immobilization or removal of cationic potentially toxic elements (PTE) in heavily polluted soils are often poorly understood, although both are widely studied in the context of phytostabilization. To address this issue, a novel compost-diatomite hybrid (CDH) amendment was developed and applied for assisted phytostabilization at two external temperature regimes. (Cd/Ni/Cu/Zn)-extremely polluted soils (unenriched and CDH-enriched) were cultivated with perennial ryegrass and native soil microbiome under greenhouse conditions and then transferred to freeze-thaw conditions (FTC). The decrease in metal potential toxicity in soils subjected to phytostabilization following both temperature treatments was characterized by a combination of sequential extraction and atomic absorption measurements. The soil microbiome was characterized by high-throughput sequencing. In a relative comparison, the greatest decrease in the content of all PTEs in CDH-enriched soil (compared to unenriched soil) appeared in FTC. Furthermore, under the influence of FTC, in the relative comparison between two CDH-enriched soils (exposed-, and not-exposed- to FTC) and two unenriched soils (exposed-, and not-exposed- to FTC), the content of all PTEs decreased more sharply in the CDH-enriched series than in the unenriched series. The largest redistribution into four sequentially extracted fractions in CDH-enriched soil was found for Zn. Based on the distribution pattern, Zn immobilization was greater in CDH-enriched soil in FTC. CDH increased species richness in the soil, while FTC stimulated the growth of Bacteroidia, Alphaproteobacteria, Theromomicrobia, and Gammaproteobacteria. The analysis of the functionalities of the microbiome indicated enhanced metal transportation and defense systems in samples exposed to FTC. The current research is crucial for understanding how extreme environmental conditions in both cases high pollutant levels and low temperatures affect the movement and transformation of PTEs in polluted soils during phytostabilization.

Time-Resolved Evaluation of L-Dopa Metabolism in Bacteria-Host Symbiotic System and the Effect on Parkinson's Molecular Pathology.

The gut microbiome influences drug metabolism and therapeutic efficacy. Still, the lack of a general label-free approach for monitoring bacterial or host metabolic contribution hampers deeper insights. Here, a 2D nuclear magnetic resonance (NMR) approach is introduced that enables real-time monitoring of the metabolism of Levodopa (L-dopa), an anti-Parkinson drug, in both live bacteria and bacteria-host (Caenorhabditis elegans) symbiotic systems. The quantitative method reveals that discrete Enterococcus faecalis substrains produce different amounts of dopamine in live hosts, even though they are a single species and all have the Tyrosine decarboxylase (TyrDC) gene involved in L-dopa metabolism. The differential bacterial metabolic activity correlates with differing Parkinson's molecular pathology concerning alpha-synuclein aggregation as well as behavioral phenotypes. The gene's existence or expression is not an indicator of metabolic activity is also shown, underscoring the significance of quantitative metabolic estimation in vivo. This simple approach is widely adaptable to any chemical drug to elucidate pharmacomicrobiomic relationships and may help rapidly screen bacterial metabolic effects in drug development.

Saliva assay: a call for methodological standardization.

The oral cavity provides an ideal environment for microorganisms, including bacteria, viruses, and fungi, to flourish. Increasing attention has been focused on the connection between the oral microbiome and both oral and systemic diseases, spurring active research into the collection and analysis of specimens for healthcare purposes. Among the various methods for analyzing the oral microbiome, saliva analysis is especially prominent. Saliva samples, which can be collected non-invasively, provide information on the systemic health and oral microbiome composition of an individual. This review was performed to evaluate the current state of the relevant research through an examination of the literature and to suggest an appropriate assay method for investigating the oral microbiome. We analyzed articles published in English in SCI(E) journals after January 1, 2000, ultimately selecting 53 articles for review. Articles were identified through keyword searches in the PubMed, Embase, Cochrane, Web of Science, and CINAHL databases. Three experienced researchers conducted full-text assessments following title and abstract screening to select appropriate papers. Subsequently, they organized and analyzed the desired data. Our review revealed that most studies utilized unstimulated saliva samples for oral microbiome analysis. Of the 53 studies examined, 29 identified relationships between the oral microbiome and various diseases, such as oral disease, Behçet disease, cancer, and oral lichen planus. However, the studies employed diverse methods of collection and analysis, which compromised the reliability and accuracy of the findings. To address the limitations caused by methodological inconsistencies, a standardized saliva assay should be established.

Fecal IgE Analyses Reveal a Role for Stratifying Peanut-Allergic Patients.

BACKGROUND AND OBJECTIVE: Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping. METHODS: Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens. RESULTS: Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes. CONCLUSION: Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function.

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

scMicrobe PTA: near complete genomes from single bacterial cells.

Microbial genomes produced by standard single-cell amplification methods are largely incomplete. Here, we show that primary template-directed amplification (PTA), a novel single-cell amplification technique, generated nearly complete genomes from three bacterial isolate species. Furthermore, taxonomically diverse genomes recovered from aquatic and soil microbiomes using PTA had a median completeness of 81%, whereas genomes from standard multiple displacement amplification-based approaches were usually <30% complete. PTA-derived genomes also included more associated viruses and biosynthetic gene clusters.

Adolescent gut microbiome imbalance and its association with immune response in inflammatory bowel diseases and obesity.

BACKGROUND: Recently, there has been an increase in the number of studies focusing on the association between the gut microbiome and obesity or inflammatory diseases, especially in adults. However, there is a lack of studies investigating the association between gut microbiome and gastrointestinal (GI) diseases in adolescents. METHOD: We obtained 16S rRNA-seq datasets for gut microbiome analysis from 202 adolescents, comprising ulcerative colitis (UC), Crohn's disease (CD), obesity (Ob), and healthy controls (HC). We utilized Quantitative Insights Into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to acquire Operational Taxonomic Units (OTUs). Subsequently, we analyzed Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO) terms and pathway enrichment for the identified OTUs. RESULTS: In this study, we investigated the difference between the gut microbiomes in adolescents with GI diseases and those in healthy adolescents using 202 samples of 16S rRNA sequencing data. The distribution of the six main gut microbiota (i.e., unclassified Dorea, unclassified Lachnospiraceae, unclassified Ruminococcus, Faecalibacterium prausnitzii, Prevotella copri, unclassified Sutterella) was different based on the status of obesity and inflammatory diseases. Dysbiosis was observed within Lachnospiraceae in adolescents with inflammatory diseases (i.e., UC and CD), and in adolescents with obesity within Prevotella and Sutterella. More specifically, our results showed that the relative abundance of Faecalibacterium prausnitzii and unclassified Lachnospiraceae was more than 10% and 8% higher, respectively, in the UC group compared to the CD, Ob, and HC groups. Additionally, the Ob group had over 20% and over 3% higher levels of Prevotella copri and unclassified Sutterella, respectively, compared to the UC, CD, and HC groups. Also, inspecting associations between the six specific microbiota and KO terms, we found that the six microbiota -relating KO terms were associated with NOD-like receptor signaling. These six taxa differences may affect the immune system and inflammatory response by affecting NOD-like receptor signaling in the host during critical adolescence. CONCLUSION: In this study, we discovered that dysbiosis of the microbial community had varying degrees of influence on the inflammatory and immune response pathways in adolescents with inflammatory diseases and obesity.

Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury.

Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.

Persistent enrichment of multidrug-resistant Klebsiella in oral and nasal communities during long-term starvation.

BACKGROUND: The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear. RESULTS: Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals' oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions. CONCLUSIONS: Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella's enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts. Video Abstract.

Rumen and hindgut microbiome regulate average daily gain of preweaning Holstein heifer calves in different ways.

BACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05). CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.

Effects of dietary zinc on the gut microbiome and resistome of the gestating cow and neonatal calf.

Zinc is an essential trace element required in the diet of all species. While the effects of zinc have been studied in growing calves, little is known about the effect of zinc on the microbiota of the gestating cow or her neonatal calf. Understanding factors that shape the gut health of neonatal animals and evaluating the effect of dietary supplements in adult gestating animals is important in promoting animal health and informing feeding practices. The aims of this study were to determine the effect of dietary zinc on the microbiota and resistome of the gestating cow and calf. Gestating cows received standard (40 ppm) or high (205 ppm) dietary zinc levels from dry off to calving. Fecal samples were collected from cows upon enrollment and at calving and from neonatal calves. Fecal samples underwent 16S rRNA sequencing and a subset also underwent shotgun metagenomic sequencing. The effect of zinc supplementation on the diversity and composition of the cow and calf microbiome and resistome was assessed. Alpha and beta diversity and composition of the microbiota were significantly altered over time but not by treatment in the cows, with alpha diversity decreasing and 14 genera found at significantly higher relative abundances at calving compared to enrollment. Levels of 27 antimicrobial resistance genes significantly increased over time. Only a small number of taxa were differentially expressed at calving in treatment and control groups, including Faecalibacterium, Bacteroides, Turicibacter, and Bifidobacterium pseudolongum. No effect of the dam's treatment group was observed on the diversity or composition of the neonatal calf microbiota. The calf resistome, which was relatively rich and diverse compared to the cow, was also unaffected by the dam's treatment group. The impact of high levels of dietary zinc thus appeared to be minimal, with no observed changes in alpha or beta diversity, and few changes in the relative abundance of a small number of taxa and antimicrobial resistance genes.

Microplastics in heavy metal-contaminated soil drives bacterial community and metabolic changes.

Microplastic (MP) and heavy metal pollution in soil are global issues. When MPs invade the soil, they combine with heavy metals and adversely affect soil organisms. Six common MPs-polyethylene, polypropylene, polystyrene, polyvinyl chloride, polyethylene terephthalate, and polytetrafluoroethylene-were selected for this study to examine the effects of various concentrations and MP types on the physicochemical properties, bacterial community, and soil metabolism of heavy metal-contaminated soil. MP enhanced predation and competition among heavy metal-contaminated soil bacteria. Heavy metal-MPs alter metabolites in lipid metabolism, other pathways, and the bacterial community. MP treatment promotes energy production and oxidative stress of soil bacteria to resist the toxicity of heavy metals and degrade MP pollution. In conclusion, MP treatment changed the metabolism of the microbiome in heavy metal-contaminated soil and increased the abundance of Proteobacteria that responded to MPs and heavy metal pollution by 11.54 % on average. This study explored bacteria for the ecological regeneration and provided ideas for MPs and heavy metal-contaminated soil remediation.

Emerging Insights into the Endocrine Regulation of Bone Homeostasis by Gut Microbiome.

Gut microbiota plays an important role in the regulation of bone homeostasis and bone health. Recent studies showed that these effects could be mediated through microbial metabolites released by the microbiota like short-chain fatty acids, metabolism of endogenous molecules such as bile acids, or a complex interplay between microbiota, the endocrine system, and the immune system. Importantly, some studies showed a reciprocal relationship between the endocrine system and gut microbiota. For instance, postmenopausal estrogen deficiency could lead to dysbiosis of the gut microbiota, which could in turn affect various immune response and bone remodeling. In addition, evidence showed that shift in the indigenous gut microbiota caused by antibiotics treatment may also impact normal skeletal growth and maturation. In this mini-review, we describe recent findings on the role of microbiome in bone homeostasis, with a particular focus on molecular mechanisms and their interactions with the endocrine and immune system. We will also discuss the recent findings on estrogen deficiency and microbiota dysbiosis, and the clinical implications for the development of new therapeutic strategies for osteoporosis and other bone disorders.

Pediococcus pentosaceus PP34 Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis via Inhibiting Oxidative Stress and Restoring the Gut Microbiota.

Chemotherapy-induced intestinal mucositis based on 5-fluorouracil (5-FU) slows down the progress of cancer treatment and causes significant suffering to patients. Pediococcus pentosaceus (P. pentosaceus), as a type of LAB, has a range of probiotic properties, including antioxidant, immune benefits, and cholesterol-lowering effects, which are attracting increasing attention. However, studies on the protective effect of P. pentosaceus against chemotherapeutic-induced intestinal mucositis caused by 5-FU remain unclear. Therefore, this study aimed to investigate the potential relieving effects of P. pentosaceus PP34 on 5-FU-induced intestinal mucositis and its mechanism. In the present study, a P. pentosaceus PP34 solution (2 × 109 CFU/mL) was administered daily by gavage followed by intraperitoneal injection of 5-FU to model intestinal mucositis. The body weight, serum biochemical indices, jejunal pathological organization, and expression levels of inflammatory cytokines in the jejunum were examined. The results indicated that the mice induced with 5-FU developed typical intestinal mucositis symptoms and histopathological changes with intense inflammatory and oxidative responses. Moreover, the gut microbiota was disturbed, while PP34 effectively decreased the oxidative reactions and the expression levels of inflammatory mediators and regulated the gut microbiota in 5-FU-exposed mice. Taken together, the study indicated that P. pentosaceus PP34 ameliorates 5-Fluorouracil-induced intestinal mucositis via inhibiting oxidative stress and restoring the gut microbiota.

Effects of antibiotics on the anti-tumor efficacy of immune checkpoint inhibitor therapy.

PURPOSE: Immunotherapy using immune checkpoint inhibitors (ICIs) has shown several benefits over traditional therapies. However, the eligible population remains small. Antibiotic (ATB) use might reduce immunotherapy efficacy by disrupting the gut microbiota. However, in China, ATB effect on ICI therapy efficacy remains unelucidated. We aimed to assess the effects of ATBs on the anti-tumor efficacy of ICIs to provide a reference for clinical use. METHODS: We included 134 patients with advanced tumors undergoing ICI therapy at Shanghai Jiading District Central Hospital from January 1, 2021, to October 1, 2023. They were divided into Non-ATB and ATB groups based on ATB use within 30 days before and after ICI administration. Moreover, we compared progression-free (PFS) and overall (OS) survival between the groups. RESULTS: Median PFS and OS were lower in the ATB than in the Non-ATB group (PFS: 4.0 vs. 5.5 months; OS: 5.4 vs. 6.5 months). Univariate analysis revealed that ATB use significantly affected PFS (hazard ratio [HR] = 2.318, 95% confidence interval [CI] = 1.281-4.194, P = 0.005) and OS (HR = 2.115, 95% CI = 1.161-3.850, P = 0.014). Moreover, multivariate analysis revealed poor PFS (HR = 2.573, 95% CI = 1.373-4.826, P = 0.003) and OS (HR = 2.452, 95% CI = 1.298-4.632, P = 0.006) in patients who received ATBs during ICI therapy. CONCLUSIONS: ATB use is negatively correlated with ICI therapy efficacy, leading to reduced PFS and OS in patients undergoing such treatment. Owing to the significant impact of ATBs on the human gut microbiome, regulation of the gut microbiome may emerge as a novel therapeutic target that can enhance the clinical activity of ICIs.

Faecal microbial diversity in a cattle herd infected by Mycobacterium avium subsp. paratuberculosis: a possible effect of production status.

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, or paratuberculosis (PTB) in ruminants, besides having zoonotic potential. It possibly changes the gut microbiome, but no conclusive data are available yet. This study aimed at investigating the influence of MAP on the faecal microbiome of cattle naturally infected with PTB. In a follow up period of 10 months, PTB status was investigated in a herd of dairy cattle with history of clinical cases. Each animal was tested for MAP infection using serum and milk ELISA for MAP anti-bodies and IS900 real-time PCR and recombinase polymerase amplification assays for MAP DNA in the faeces and milk monthly for 4 successive months, then a last one after 6 months. The faecal samples were subjected to 16S rDNA metagenomic analysis using Oxford Nanopore Sequencing Technology. The microbial content was compared between animal groups based on MAP positivity rate and production status. All animals were MAP positive by one or more tests, but two animals were consistently negative for MAP DNA in the faeces. In all animals, the phyla firmicutes and bacteroidetes were highly enriched with a small contribution of proteobacteria, and increased abundance of the families Oscillospiraceae, Planococcaceae, and Streptococcacaceae was noted. Animals with high MAP positivity rate showed comparable faecal microbial content, although MAP faecal positivity had no significant effect (p > 0.05) on the microbiome. Generally, richness and evenness indices decreased with increasing positivity rate. A significantly different microbial content was found between dry cows and heifers (p < 0.05). Particularly, Oscillospiraceae and Rikenellaceae were enriched in heifers, while Planococcaceae and Streptococcaceae were overrepresented in dry cows. Furthermore, abundance of 72 genera was significantly different between these two groups (p < 0.05). Changes in faecal microbiome composition were notably associated with increasing MAP shedding in the faeces. The present findings suggest a combined influence of the production status and MAP on the cattle faecal microbiome. This possibly correlates with the fate of the infection, the concern in disease control, again remains for further investigations.