Intestinal Blastocystis is linked to healthier diets and more favorable cardiometabolic outcomes in 56,989 individuals from 32 countries.

Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.

Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire.

Phage-displayed immunoprecipitation sequencing (PhIP-seq) has enabled high-throughput profiling of human antibody repertoires. However, a comprehensive overview of environmental and genetic determinants shaping human adaptive immunity is lacking. In this study, we investigated the effects of genetic, environmental, and intrinsic factors on the variation in human antibody repertoires. We characterized serological antibody repertoires against 344,000 peptides using PhIP-seq libraries from a wide range of microbial and environmental antigens in 1,443 participants from a population cohort. We detected individual-specificity, temporal consistency, and co-housing similarities in antibody repertoires. Genetic analyses showed the involvement of the HLA, IGHV, and FUT2 gene regions in antibody-bound peptide reactivity. Furthermore, we uncovered associations between phenotypic factors (including age, cell counts, sex, smoking behavior, and allergies, among others) and particular antibody-bound peptides. Our results indicate that human antibody epitope repertoires are shaped by both genetics and environmental exposures and highlight specific signatures of distinct phenotypes and genotypes.

Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures.

Inflammatory bowel diseases (IBDs), e.g., Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. Using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq), we identified antibodies against 344,000 antimicrobial, immune, and food antigens in 497 individuals with IBD compared with 1,326 controls. IBD was characterized by 373 differentially abundant antibody responses (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD, and 28% unique to UC. Antibody reactivities against bacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenotic disease, and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitope repertoires accurately discriminated CD from controls (area under the curve [AUC] = 0.89), and similar discrimination was achieved when using only ten antibodies (AUC = 0.87). Individuals with IBD thus show a distinct antibody repertoire against selected peptides, allowing clinical stratification and discovery of immunological targets.

Host genetic regulation of human gut microbial structural variation.

Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established1-6, little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort. In vitro experiments demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. Further in silico and in vitro studies demonstrated that other ABO-associated species can also utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc utilization genes are also associated with the host's cardiometabolic health, particularly in individuals with mucosal A-antigen. Together, the findings of our study demonstrate that genetic associations across the human genome and bacterial metagenome can provide functional insights into the reciprocal host-microbiome relationship.

Dense sampling of bird diversity increases power of comparative genomics.

Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.

Reproducible gut microbial signatures in bipolar and schizophrenia spectrum disorders: A metagenome-wide study.

BACKGROUND: Numerous studies report gut microbiome variations in bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) compared to healthy individuals, though, there is limited consensus on which specific bacteria are associated with these disorders. METHODS: In this study, we performed a comprehensive metagenomic shotgun sequencing analysis in 103 Dutch patients with BD/SSD and 128 healthy controls matched for age, sex, body mass index and income, while accounting for diet quality, transit time and technical confounders. To assess the replicability of the findings, we used two validation cohorts (total n = 203), including participants from a distinct population with a different metagenomic isolation protocol. RESULTS: The gut microbiome of the patients had a significantly different ß-diversity, but not α-diversity nor neuroactive potential compared to healthy controls. Initially, twenty-six bacterial taxa were identified as differentially abundant in patients. Among these, the previously reported genera Lachnoclostridium and Eggerthella were replicated in the validation cohorts. Employing the CoDaCoRe learning algorithm, we identified two bacterial balances specific to BD/SSD, which demonstrated an area under the receiver operating characteristic curve (AUC) of 0.77 in the test dataset. These balances were replicated in the validation cohorts and showed a positive association with the severity of psychiatric symptoms and antipsychotic use. Last, we showed a positive association between the relative abundance of Klebsiella and Klebsiella pneumoniae with antipsychotic use and between the Anaeromassilibacillus and lithium use. CONCLUSIONS: Our findings suggest that microbial balances could be a reproducible method for identifying BD/SSD-specific microbial signatures, with potential diagnostic and prognostic applications. Notably, Lachnoclostridium and Eggerthella emerge as frequently occurring bacteria in BD/SSD. Last, our study reaffirms the previously established link between Klebsiella and antipsychotic medication use and identifies a novel association between Anaeromassilibacillus and lithium use.

Detection of echinostomatid trematode eggs at the forest-oil palm interface in Sabah, Malaysia.

In this study, we report the occurrence of echinostomatid eggs in feces of wildlife, domestic animals and humans frequenting the forest­oil palm plantation interface in the Kinabatangan (Sabah, Malaysia), and discuss potential implications for public health. Using microscopy, we detected echinostomatid eggs in six host species, including Asian palm civets (Paradoxurus hermaphroditus [13/18]), leopard cats (Prionailurus bengalensis [3/4]), long-tailed macaques (Macaca fascicularis [1/10]), domestic dogs [3/5] and cats [1/1], and humans [7/9]. Molecular analysis revealed a close genetic proximity of civet echinostomatids to Artyfechinostomum malayanum, a zoonotic parasite of public health relevance. The intermediate hosts for A. malayanum have been reported in at least 3 districts in Sabah, suggesting that all the necessary elements required for the completion of the parasite's life cycle are present. Our findings point at the presence of zoonotic trematodes in an area with high human­wildlife interaction and highlight the potential public and animal health concern of zoonotic trematode infection in the context of Southeast Asia's rapidly changing ecosystems.

An overview of the two-component system GarR/GarS role on antibiotic production in Streptomyces coelicolor.

The Streptomyces genus comprises Gram-positive bacteria known to produce over two-thirds of the antibiotics used in medical practice. The biosynthesis of these secondary metabolites is highly regulated and influenced by a range of nutrients present in the growth medium. In Streptomyces coelicolor, glucose inhibits the production of actinorhodin (ACT) and undecylprodigiosin (RED) by a process known as carbon catabolite repression (CCR). However, the mechanism mediated by this carbon source still needs to be understood. It has been observed that glucose alters the transcriptomic profile of this actinobacteria, modifying different transcriptional regulators, including some of the one- and two-component systems (TCSs). Under glucose repression, the expression of one of these TCSs SCO6162/SCO6163 was negatively affected. We aimed to study the role of this TCS on secondary metabolite formation to define its influence in this general regulatory process and likely establish its relationship with other transcriptional regulators affecting antibiotic biosynthesis in the Streptomyces genus. In this work, in silico predictions suggested that this TCS can regulate the production of the secondary metabolites ACT and RED by transcriptional regulation and protein-protein interactions of the transcriptional factors (TFs) with other TCSs. These predictions were supported by experimental procedures such as deletion and complementation of the TFs and qPCR experiments. Our results suggest that in the presence of glucose, the TCS SCO6162/SCO6163, named GarR/GarS, is an important negative regulator of the ACT and RED production in S. coelicolor. KEY POINTS: • GarR/GarS is a TCS with domains for signal transduction and response regulation • GarR/GarS is an essential negative regulator of the ACT and RED production • GarR/GarS putatively interacts with and regulates activators of ACT and RED.

Influence of a football match on landing biomechanics and jump performance in female football players.

This study aimed to assess the acute effect of a competitive football match on jump performance and kinematic parameters during jump landing in semiprofessional female football players. Twenty-two semiprofessional players (20 ± 3 years) underwent a drop jump task for a posterior video analysis of the landing phase. These measurements were obtained at (1) baseline, (2) after, and (3) 48 h after a competitive football match. A one-way ANOVA with repeated measures was employed to detect differences over the time. There was a main effect of time for maximal knee flexion angle during drop landing (p = 0.001). In comparison with baseline, maximal knee flexion angle was reduced immediately post-match and was still reduced 48 h after the match (63.4 ± 8.6 vs 57.0 ± 11.7 vs 48.9 ± 19.1, p ≤ 0.038). There was also a main effect of time for drop jump height (p < 0.001). Drop jump height was reduced immediately post-match and remained low 48 h after the match in comparison with baseline (27.3 ± 3.6 vs 24.5 ± 2.8 ~ 25.5 ± 3.0 cm, p ≤ 0.002). There was a main effect of time on hip flexion angle during landing (p = 0.001), but the pairwise comparison revealed that this variable was not affected immediately post-match but was lower 48 h after the match than at baseline (50.1 ± 10.1 ~ 50.8 ± 13.2 vs 38.1 ± 17.8 °, p ≤ 0.005). A competitive football match worsened jump performance and several landing biomechanical parameters in female football players, which were still decreased in comparison with baseline even 48 h after the match.

HPLC-Based Metabolomic Analysis and Characterization of Amaranthus cruentus Leaf and Inflorescence Extracts for Their Antidiabetic and Antihypertensive Potential.

The aim of this study was to investigate the potential of Amaranthus cruentus flavonoids (quercetin, kaempferol, catechin, hesperetin, naringenin, hesperidin, and naringin), cinnamic acid derivatives (p-coumaric acid, ferulic acid, and caffeic acid), and benzoic acids (vanillic acid and 4-hydroxybenzoic acid) as antioxidants, antidiabetic, and antihypertensive agents. An analytical method for simultaneous quantification of flavonoids, cinnamic acid derivatives, and benzoic acids for metabolomic analysis of leaves and inflorescences from A. cruentus was developed with HPLC-UV-DAD. Evaluation of linearity, limit of detection, limit of quantitation, precision, and recovery was used to validate the analytical method developed. Maximum total flavonoids contents (5.2 mg/g of lyophilized material) and cinnamic acid derivatives contents (0.6 mg/g of lyophilized material) were found in leaves. Using UV-Vis spectrophotometry, the maximum total betacyanin contents (74.4 mg/g of lyophilized material) and betaxanthin contents (31 mg/g of lyophilized material) were found in inflorescences. The leaf extract showed the highest activity in removing DPPH radicals. In vitro antidiabetic activity of extracts was performed with pancreatic α-glucosidase and intestinal α-amylase, and compared to acarbose. Both extracts exhibited a reduction in enzyme activity from 57 to 74%. Furthermore, the in vivo tests on normoglycemic murine models showed improved glucose homeostasis after sucrose load, which was significantly different from the control. In vitro antihypertensive activity of extracts was performed with angiotensin-converting enzyme and contrasted to captopril; both extracts exhibited a reduction of enzyme activity from 53 to 58%. The leaf extract induced a 45% relaxation in an ex vivo aorta model. In the molecular docking analysis, isoamaranthin and isogomphrenin-I showed predictive binding affinity for α-glucosidases (human maltase-glucoamylase and human sucrase-isomaltase), while catechin displayed binding affinity for human angiotensin-converting enzyme. The data from this study highlights the potential of A. cruentus as a functional food.

Peat-based amendment of soils reduces the complexity of the volatile profile in cultivated black truffles.

BACKGROUND: Truffle cultivation is evolving rapidly and new agronomic practices such as 'truffle nests' (localized peat amendments of the orchard soil) are being developed. Truffle nests improve the shape of truffles and their depth in the soil and reduce the occurrence of insect damage but have also raised concerns about their impact on the ripeness and maturity of the harvested truffles. In this study, the effect of the nests on the volatile organic compounds profile and the aromatic profile of black truffles was evaluated, as well as the existence of perceptible sensorial differences in truffles. For this, truffles growing in nests were compared with truffles growing in the bulk soil of the same host tree. RESULTS: Gas chromatography showed that nest truffles had a less complex volatile organic compound profile than bulk-soil truffles. Olfactometry indicated that nest truffles were associated with higher modified frequency values of odorants corresponding to sulfur-containing compounds. Despite this, sensory evaluation with consumers could not clearly show that nest truffles can be distinguished sensorially from bulk-soil truffles. CONCLUSION: The results prove that soil conditions can influence the aromatic profile of truffles and thus suggest the possibility of managing truffle aroma using agronomic practices. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Spanish Cross-Cultural Adaptation and Validation of the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score.

CONTEXT: There are no available questionnaires in Spanish that assess the function and performance of shoulder and elbow in overhead sports. The Kerlan-Jobe Orthopaedic Clinic (KJOC) score is a reference tool for this purpose. We aimed to cross-culturally adapt and investigate its measurement properties in Spanish overhead athletes. DESIGN: Cross-cultural adaptation followed the steps of direct translation, back translation, comprehensibility analysis, and review by the Committee of Experts. Then, symptomatic and asymptomatic overhead athletes were invited to complete an electronic version of the Spanish adaptation (KJOC-Sp). The structural validity was evaluated through an exploratory factor analysis with principal axis factoring. Hypotheses were tested for known-groups and convergent validity, studying the correlation with the Shoulder Pain and Disability Index and the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaires in symptomatic athletes. Cronbach alpha was calculated for internal consistency and intraclass correlation coefficient (ICC)2,1 for test-retest reliability. Floor and ceiling effects and time to completion were also calculated. RESULTS: The KJOC-Sp maintained the content of the original version and was adapted to the new population. One hundred participants (41 females and 59 males) with a mean age of 22.4 (5.9) years participated in the study of measurement properties. The factor analysis revealed a 1-factor solution. Symptomatic participants scored significantly lower than asymptomatic, with a large effect size (P < .001; r = .67). Correlations were of -.60 (P < .05) with the Shoulder and Pain Disability Index questionnaire and -0.66 (P < .05) with the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaire. Cronbach alpha was .98 (95% confidence interval, .97-.98) and the ICC2,1 was .96 (95% confidence interval .93-.98). No floor or ceiling effects were observed among the symptomatic athletes, while mean time to completion was 121 seconds. CONCLUSION: The KJOC-Sp is equivalent to the original score, aside from valid and reliable, without floor or ceiling effects in symptomatic athletes and with a low time consumption.

Faecal metabolome and its determinants in inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD. DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels. RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism. CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.

Selective enrichment of founding reproductive microbiomes allows extensive vertical transmission in a fungus-farming termite.

Mutualistic coevolution can be mediated by vertical transmission of symbionts between host generations. Termites host complex gut bacterial communities with evolutionary histories indicative of mixed-mode transmission. Here, we document that vertical transmission of gut bacterial strains is congruent across parent to offspring colonies in four pedigrees of the fungus-farming termite Macrotermes natalensis. We show that 44% of the offspring colony microbiome, including more than 80 bacterial genera and pedigree-specific strains, are consistently inherited. We go on to demonstrate that this is achieved because colony-founding reproductives are selectively enriched with a set of non-random, environmentally sensitive and termite-specific gut microbes from their colonies of origin. These symbionts transfer to offspring colony workers with high fidelity, after which priority effects appear to influence the composition of the establishing microbiome. Termite reproductives thus secure transmission of complex communities of specific, co-evolved microbes that are critical to their offspring colonies. Extensive yet imperfect inheritance implies that the maturing colony benefits from acquiring environmental microbes to complement combinations of termite, fungus and vertically transmitted microbes; a mode of transmission that is emerging as a prevailing strategy for hosts to assemble complex adaptive microbiomes.

Identification and validation of novel Blastocystis subtype ST41 in a Colombian patient undergoing colorectal cancer screening.

Blastocystis sp. is among the most frequent intestinal protists identified in humans globally. However, characterization of Blastocystis subtype diversity in humans is ongoing. We report here the identification of novel Blastocystis subtype ST41 in a Colombian patient undergoing colorectal cancer screening involving colonoscopy and fecal testing (microscopy, culture, PCR). The full-length ssu rRNA gene sequence of the protist was generated using MinION long-read sequencing technology. The validity of the novel subtype was confirmed via phylogenetic and pairwise distance analyses of the full-length ST41 sequence and all other valid subtypes. The study provides reference material essential for conducting subsequent experimental studies.

Intraspecific Competition Results in Reduced Evenness of Tuber melanosporum Mating-Type Abundance from the Nursery Stage.

The highly prized black truffle is a fungus mostly harvested in orchards planted with mycorrhizal seedlings. It is an obligatory outcrossing fungus with a single MAT locus containing two alternative mating-type idiomorphs. In the orchards, at the mycorrhizal level, these mating types are frequently spatially segregated. Some studies found that this segregation was pronounced from the nursery stage, whereas others did not find such a marked segregation. Besides, information on the host tree species and nursery conditions used in Spain, one of the main truffle-producing countries, are very scarce. In this study, we investigated the temporal dynamics of mating types in nursery seedlings of Quercus ilex and Quercus faginea, as well as the influence of cultural conditions in the nursery. Our results indicated that at the plant level, there was a trend for one of the mating types to dominate over the other from the first to the second year in the nursery, in both host species and both nursery conditions tested. However, this segregation process was not so sharp as previously reported. Our results support the hypothesis that intraspecific competition results in reduced evenness of mating-type abundance from the nursery stage, although almost all seedlings maintained both mating types and, at the seedling batch scale, the occurrence of both mating types was roughly balanced.

"Don't add fuel to the fire"- Hyperhemolysis Syndrome in a pregnant woman with compound Sickle cell disease/ß0-thalassemia - Case report and review of the literature.

Hyperhemolysis Syndrome (HHS) is a rare and severe post-transfusion complication characterized by the destruction of both recipient and donor red blood cells (RBC). The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound Sickle cell disease/ß-0-thalassemia after transfusion of not fully compatible packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration.

The untapped potential of actinobacterial lanthipeptides as therapeutic agents.

The increase in bacterial resistance generated by the indiscriminate use of antibiotics in medical practice set new challenges for discovering bioactive natural products as alternatives for therapeutics. Lanthipeptides are an attractive natural product group that has been only partially explored and shows engaging biological activities. These molecules are small peptides with potential application as therapeutic agents. Some members show antibiotic activity against problematic drug-resistant pathogens and against a wide variety of viruses. Nevertheless, their biological activities are not restricted to antimicrobials, as their contribution to the treatment of cystic fibrosis, cancer, pain symptoms, control of inflammation, and blood pressure has been demonstrated. The study of biosynthetic gene clusters through genome mining has contributed to accelerating the discovery, enlargement, and diversification of this group of natural products. In this review, we provide insight into the recent advances in the development and research of actinobacterial lanthipeptides that hold great potential as therapeutics.

Trends in the two-component system's role in the synthesis of antibiotics by Streptomyces.

Despite the advances in understanding the regulatory networks for secondary metabolite production in Streptomyces, the participation of the two-component systems (TCS) in this process still requires better characterization. These sensing systems and their responses to environmental stimuli have been described by evaluating mutant strains with techniques that allow in-depth regulatory responses. However, defining the stimulus that triggers their activation is still a task. The transmembrane nature of the sensor kinases and the high content of GC in the streptomycetes represent significant challenges in their study. In some examples, adding elements to the assay medium has determined the respective ligand. However, a complete TCS description and characterization requires specific amounts of the involved proteins that are most difficult to obtain. The availability of enough sensor histidine kinase concentrations could facilitate the identification of the ligand-protein interaction, and besides would allow the establishment of its phosphorylation mechanisms and determine their tridimensional structure. Similarly, the advances in the development of bioinformatics tools and novel experimental techniques also promise to accelerate the TCSs description and provide knowledge on their participation in the regulation processes of secondary metabolite formation. This review aims to summarize the recent advances in the study of TCSs involved in antibiotic biosynthesis and to discuss alternatives to continue their characterization. KEY POINTS: • TCSs are the environmental signal transducers more abundant in nature. • The Streptomyces have some of the highest number of TCSs found in bacteria. • The study of signal transduction between SHKs and RRs domains is a big challenge.

Opportunities and challenges of microbial siderophores in the medical field.

Siderophores are low-molecular-weight secondary metabolites that function as iron chelators. Under iron-deficiency conditions, they are produced by a wide variety of microbes, allowing them to increase their iron uptake. The primary function of these compounds is the environmental iron scavenging and its transport into the cytosol. Iron is then reduced to its ferrous form to operate as an enzymatic cofactor for various functions, including respiration, nitrogen fixation, photosynthesis, methanogenesis, and amino acid synthesis. Depending on their functional group, siderophores are classified into hydroxamate, catecholate, phenolate, carboxylate, and mixed types. They have achieved great importance in recent years due to their medical applications as antimicrobial, antimalarial, or anticancer drugs, vaccines, and drug-delivery agents. This review integrates current advances in specific healthcare applications of microbial siderophores, delineating new opportunities and challenges as viable therapies to fight against diseases that represent crucial public health problems in the medical field.Key points• Siderophores are low-molecular-weight secondary metabolites functioning as iron chelators.• The siderophore's properties offer viable options to face diverse clinical problems.• Siderophores are alternatives for the enhancement of antibiotic activities.