Metagenomic insights into fungal community composition of the nasopharyngeal region of COVID-19 associated mucormycosis patients from India.

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.

Collinsella aerofaciens linked with increased ethanol production and liver inflammation contribute to the pathophysiology of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD.

Genomic and functional insights into antibiotic resistance genes floR and strA linked with the SXT element of Vibrio cholerae non-O1/non-O139.

The emergence and spread of antibiotic-resistant bacterial pathogens are a critical public health concern across the globe. Mobile genetic elements (MGEs) play an important role in the horizontal acquisition of antimicrobial resistance genes (ARGs) in bacteria. In this study, we have decoded the whole genome sequences of multidrug-resistant Vibrio cholerae clinical isolates carrying the ARG-linked SXT, an integrative and conjugative element, in their large chromosomes. As in others, the SXT element has been found integrated into the 5'-end of the prfC gene (which encodes peptide chain release factor 3 involved in translational regulation) on the large chromosome of V. cholerae non-O1/non-O139 strains. Further, we demonstrate the functionality of SXT-linked floR and strAB genes, which confer resistance to chloramphenicol and streptomycin, respectively. The floR gene-encoded protein FloR belongs to the major facilitator superfamily efflux transporter containing 12 transmembrane domains (TMDs). Deletion analysis confirmed that even a single TMD of FloR is critical for the export function of chloramphenicol. The floR gene has two putative promoters, P1 and P2. Sequential deletions reveal that P2 is responsible for the expression of the floR. Deletion analysis of the N- and/or C-terminal coding regions of strA established their importance for conferring resistance against streptomycin. Interestingly, qPCR analysis of the floR and strA genes indicated that both of the genes are constitutively expressed in V. cholerae cells. Further, whole genome-based global phylogeography confirmed the presence of the integrative and conjugative element SXT in non-O1/non-O139 strains despite being non-multidrug resistant by lacking antimicrobial resistance (AMR) gene cassettes, which needs monitoring.

Antibiotic Potentiation as a Promising Strategy to Combat Macrolide Resistance in Bacterial Pathogens.

Antibiotics, which hit the market with astounding impact, were once called miracle drugs, as these were considered the ultimate cure for infectious diseases in the mid-20th century. However, today, nearly all bacteria that afflict humankind have become resistant to these wonder drugs once developed to stop them, imperiling the foundation of modern medicine. During the COVID-19 pandemic, there was a surge in macrolide use to treat secondary infections and this persistent use of macrolide antibiotics has provoked the emergence of macrolide resistance. In view of the current dearth of new antibiotics in the pipeline, it is essential to find an alternative way to combat drug resistance. Antibiotic potentiators or adjuvants are non-antibacterial active molecules that, when combined with antibiotics, increase their activity. Thus, potentiating the existing antibiotics is one of the promising approaches to tackle and minimize the impact of antimicrobial resistance (AMR). Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against multidrug-resistant (MDR) pathogens. The present review summarizes the different resistance mechanisms adapted by bacteria to resist macrolides and further emphasizes the major macrolide potentiators identified which could serve to revive the antibiotic and can be used for the reversal of macrolide resistance.

Host microbiome in tuberculosis: disease, treatment, and immunity perspectives.

Tuberculosis (TB), an airborne pulmonary disease caused by Mycobacterium tuberculosis (M. tb), poses an unprecedented health and economic burden to most of the developing countries. Treatment of TB requires prolonged use of a cocktail of antibiotics, which often manifest several side effects, including stomach upset, nausea, and loss of appetite spurring on treatment non-compliance and the emergence of antibiotic resistant M. tb. The anti-TB treatment regimen causes imbalances in the composition of autochthonous microbiota associated with the human body, which also contributes to major side effects. The microbiota residing in the gastrointestinal tract play an important role in various physiological processes, including resistance against colonization by pathogens, boosting host immunity, and providing key metabolic functions. In TB patients, due to prolonged exposure to anti-tuberculosis drugs, the gut microbiota significantly loses its diversity and several keystone bacterial taxa. This loss may result in a significant reduction in the functional potency of the microbiota, which is a probable reason for poor treatment outcomes. In this review, we discuss the structural and functional changes of the gut microbiota during TB and its treatment. A major focus of the review is oriented to the gut microbial association with micronutrient profiles and immune cell dynamics during TB infection. Furthermore, we summarize the acquisition of anti-microbial resistance in M. tb along with the microbiome-based therapeutics to cure the infections. Understanding the relationship between these components and host susceptibility to TB disease is important to finding potential targets that may be used in TB prevention, progression, and cure.

Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice.

A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.

Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

Post-COVID-19 rhino-orbito-cerebral mucormycosis-A clinico-mycological study from North India.

The second wave of coronavirus disease 2019 (COVID-19), during the early 2021, lead to a devastating outbreak of mucormycosis in India. This study aimed to determine the aetiology, clinical features, comorbidities, and risk factors of rhino-orbito-cerebral mucormycosis (ROCM) and antifungal susceptibility pattern for the isolates. The study included all suspected cases of ROCM in post-COVID-19 patients attending the hospital from May to December 2021. A total of 70 patients were diagnosed with mucormycosis during the study period. The commonest presentations were rhino-orbital and rhino-orbito-cerebral in 35.7% of cases each. Diabetes mellitus was the commonest associated risk factor in 95.7% of all patients, while 78.5% of the patients were treated with corticosteroids in the recent past, and 25.7% presented with active COVID-19 pneumonia. The commonest isolate was Rhizopus arrhizus n = 14, followed by Aspergillus flavus n = 16, A. fumigatus n = 4, A. niger n = 3, Fusarium oxysporumn = 1, and Apophysomyces variabilisn = 1. Fungal species identification was done by phenotypic methods for all the isolates and DNA sequence analysis of 18 isolates, and antifungal susceptibility testing of 30 isolates was performed by commercially prepared HiMIC plate (HiMedia, Mumbai, India) using broth microdilution for amphotericin B, isavuconazole, itraconazole, voriconazole, and posaconazole. The MIC50 and MIC90 of amphotericin B for R. arrhizus strains were 0.25 and 4 µg/ml, respectively; and the MIC50 and MIC90 results for itraconazole, posaconazole, and isavuconazole were 8 and 8, 2 and 2, and 2 and 8 µg/ml, respectively. In vitro data showed that amphotericin B was the most effective antifungal against most species. The commercially available ready-to-use minimum inhibitory concentration plates are user-friendly for performing antifungal susceptibility, which may be useful in choosing appropriate regimens and monitoring emerging resistance.

Association of gut microbial dysbiosis with disease severity, response to therapy and disease outcomes in Indian patients with COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay. RESULTS: The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes. CONCLUSION: Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.

Study on Effects of Probiotics on Gut Microbiome and Clinical Course in Patients with Critical Care Illnesses.

Ventilator-associated pneumonia (VAP) is a nosocomial infection contracted by ventilator patients in which bacteria colonize the upper digestive tract and contaminated secretions are released into the lower airway. This nosocomial infection increases the morbidity and mortality of the patients as well as the cost of treatment. Probiotic formulations have recently been proposed to prevent the colonization of these pathogenic bacteria. In this prospective observational study, we aimed to investigate the effects of probiotics on gut microbiota and their relation to clinical outcomes in mechanically ventilated patients. For this study, 35 patients were recruited (22 probiotic-treated and 13 without probiotic treatment) from a cohort of 169 patients. Patients in the probiotic group were given a dose of 6 capsules of a commercially available probiotic (VSL#3®:112.5 billion CFU/cap) in three divided doses for 10 days. Sampling was carried out after each dose to monitor the temporal change in the gut microbiota composition. To profile the microbiota, we used a 16S rRNA metagenomic approach, and differences among the groups were computed using multivariate statistical analyses. Differences in gut microbial diversity (Bray Curtis and Jaccard distance, p-value > 0.05) between the probiotic-treated group and the control group were not observed. Furthermore, treatment with probiotics resulted in the enrichment of Lactobacillus and Streptococcus in the gut microbiota of the probiotic-treated groups. Our results demonstrated that probiotics might lead to favorable alterations in gut microbiome characteristics. Future studies should focus on the appropriate dosages and frequency of probiotics, which can lead to improved clinical outcomes.

Microbiota and epigenetics: Health impact.

Epigenetic changes associated with disease development and progressions are of increasing importance because of their potential diagnostic and therapeutic applications. Several epigenetic changes associated with chronic metabolic disorders have been studied in various diseases. Epigenetic changes are mostly modulated by environmental factors, including the human microbiota living in different parts of our bodies. The microbial structural components and the microbially derived metabolites directly interact with host cells, thereby maintaining homeostasis. Microbiome dysbiosis, on the other hand, is known to produce elevated levels of disease-linked metabolites, which may directly affect a host metabolic pathway or induce epigenetic changes that can lead to disease development. Despite their important role in host physiology and signal transduction, there has been little research into the mechanics and pathways associated with epigenetic modifications. This chapter focuses on the relationship between microbes and their epigenetic effects in diseased pathology, as well as on the regulation and metabolism of the dietary options available to the microbes. Furthermore, this chapter also provides a prospective link between these two important phenomena, termed "Microbiome and Epigenetics."

Genomic insights into extensively drug-resistant Pseudomonas aeruginosa isolated from a diarrhea case in Kolkata, India.

Aim: To characterize extensively drug-resistant Pseudomonas aeruginosa from a patient with diarrhea. Materials & methods: Antimicrobial susceptibility was tested by the disk diffusion method. The P. aeruginosa genome was sequenced to identify virulence, antibiotic resistance and prophages encoding genes. Results: P. aeruginosa had a wide spectrum of resistance to antibiotics. Genomic analysis of P. aeruginosa revealed 76 genes associated with antimicrobial resistance, xenobiotic degradation and the type three secretion system. Conclusion: This is the first report on diarrhea associated with P. aeruginosa. Since no other organism was identified, the authors assume that the patient had dysbiosis due to antibiotic exposure, leading to antibiotic-associated diarrhea. The in vivo toxicity expressed by the pathogen may be associated with T3SS.

Ancestral SARS-CoV-2-Driven Antibody Repertoire Diversity in an Unvaccinated Individual Correlates with Expanded Neutralization Breadth.

Understanding the quality of immune repertoire triggered during natural infection can provide vital clues that form the basis for development of a humoral immune response in some individuals capable of broadly neutralizing pan-SARS-CoV-2 variants. In the present study, we report variations in neutralization potential against Omicron variants of two novel neutralizing monoclonal antibodies (MAbs), THSC20.HVTR11 and THSC20.HVTR55, isolated from an unvaccinated convalescent individual that represent distinct B cell lineage origins and epitope specificity compared to five MAbs we previously reported that were isolated from the same individual. In addition, we observed neutralization of Omicron variants by plasma antibodies obtained from this particular individual postvaccination with increased magnitude. Interestingly, this observation was found to be comparable with six additional individuals who initially were also infected with ancestral SARS-CoV-2 and then received vaccines, indicating that hybrid immunity can provide robust humoral immunity likely by antibody affinity maturation. Development of a distinct antigen-specific B cell repertoire capable of producing polyclonal antibodies with distinct affinity and specificities offers the highest probability of protecting against evolving SARS-CoV-2 variants. IMPORTANCE Development of robust neutralizing antibodies in SARS-CoV-2 convalescent individuals is known; however, it varies at the population level. We isolated monoclonal antibodies from an individual infected with ancestral SARS-CoV-2 in early 2020 that not only varied in their B cell lineage origin but also varied in their capability and potency to neutralize all the known variants of concern (VOCs) and currently circulating Omicron variants. This indicated establishment of unique lineages that contributed in forming a B cell repertoire in this particular individual immediately following infection, giving rise to diverse antibody responses that could complement each other in providing a broadly neutralizing polyclonal antibody response. Individuals who were able to produce polyclonal antibody responses with higher magnitude have a higher chance of being protected from evolving SARS-CoV-2 variants.

Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis.

OBJECTIVES: Prevotella copri is considered to be a contributing factor in rheumatoid arthritis (RA). However, in some non-Westernised countries, healthy individuals also harbour an abundance of P. copri in the intestine. This study investigated the pathogenicity of RA patient-derived P. copri (P. copri RA) compared with healthy control-derived P. copri (P. copri HC). METHODS: We obtained 13 P. copri strains from the faeces of patients with RA and healthy controls. Following whole genome sequencing, the sequences of P. copri RA and P. copri HC were compared. To analyse the arthritis-inducing ability of P. copri, we examined two arthritis models (1) a collagen-induced arthritis model harbouring P. copri under specific-pathogen-free conditions and (2) an SKG mouse arthritis model under P. copri-monocolonised conditions. Finally, to evaluate the ability of P. copri to activate innate immune cells, we performed in vitro stimulation of bone marrow-derived dendritic cells (BMDCs) by P. copri RA and P. copri HC. RESULTS: Comparative genomic analysis revealed no apparent differences in the core gene contents between P. copri RA and P. copri HC, but pangenome analysis revealed the high genome plasticity of P. copri. We identified a P. copri RA-specific genomic region as a conjugative transposon. In both arthritis models, P. copri RA-induced more severe arthritis than P. copri HC. In vitro BMDC stimulation experiments revealed the upregulation of IL-17 and Th17-related cytokines (IL-6, IL-23) by P. copri RA. CONCLUSION: Our findings reveal the genetic diversity of P. copri, and the genomic signatures associated with strong arthritis-inducing ability of P. copri RA. Our study contributes towards elucidation of the complex pathogenesis of RA.

Human Gut Microbiota and Drug Metabolism.

The efficacy of drugs widely varies in individuals, and the gut microbiota plays an important role in this variability. The commensal microbiota living in the human gut encodes several enzymes that chemically modify systemic and orally administered drugs, and such modifications can lead to activation, inactivation, toxification, altered stability, poor bioavailability, and rapid excretion. Our knowledge of the role of the human gut microbiome in therapeutic outcomes continues to evolve. Recent studies suggest the existence of complex interactions between microbial functions and therapeutic drugs across the human body. Therapeutic drugs or xenobiotics can influence the composition of the gut microbiome and the microbial encoded functions. Both these deviations can alter the chemical transformations of the drugs and hence treatment outcomes. In this review, we provide an overview of (i) the genetic ecology of microbially encoded functions linked with xenobiotic degradation; (ii) the effect of drugs on the composition and function of the gut microbiome; and (iii) the importance of the gut microbiota in drug metabolism.

Human Milk Microbiome of Healthy Indian Mothers is Dominated by Genus Pseudomonas.

BACKGROUND: The composition of the human milk microbiome is highly variable and multifactorial. Milk microbiota from various countries show striking differences. There is a paucity of data from healthy lactating Indian mothers. RESEARCH AIM: To describe the milk microbiota of healthy North Indian women, using a culture-independent, targeted metagenomic approach. METHODS: We recruited exclusively breastfeeding mothers (N = 22) who had vaginally delivered full-term singleton infants in a tertiary care hospital less than 1 week previously and had not recently consumed systemic antibiotics. Milk samples (5 ml) were collected aseptically, and microbial deoxyribonucleic acid was extracted. Microbial composition and diversity were determined using a 454-pyrosequencing platform. Core genera were identified, and their relative abundances ranked. Heatmaps showing the variation of the ranked abundances and Shannon index were obtained using R. RESULTS: Participants (all exclusively vegetarian) had a mean (SD) age of 27.2 (3.4) years, postnatal age of 3.9 (1.6) days and gestation 38 (1.2) weeks. The dominant phylum was Proteobacterium (relative abundance 84%) and dominant genus Pseudomonas (relative abundance 61.78%). Eleven species of Pseudomonas were identified, all generally considered nonpathogenic. Based on abundance patterns of the core genera, the milk samples could be grouped: (a) dominated by Pseudomonas with low diversity; (b) less Pseudomonas and high diversity; and (c) dominated by Pseudomonas but high diversity. All neonates were healthy and gaining weight well at 1 month of age. CONCLUSIONS: Healthy, lactating, vegetarian, North Indian women who deliver at term gestation and have no recent exposure to antibiotics, have a unique milk microbiome dominated by Pseudomonas.

Dysbiosis of the Beneficial Gut Bacteria in Patients with Parkinson's Disease from India.

Objectives: Recent advancement in understanding neurological disorders has revealed the involvement of dysbiosis of the gut microbiota in the pathophysiology of Parkinson's disease (PD). We sequenced microbial DNA using fecal samples collected from PD cases and healthy controls (HCs) to evaluate the role of gut microbiota. Methods: Full-length bacterial 16S rRNA gene sequencing of fecal samples was performed using amplified polymerase chain reaction (PCR) products on the GridION Nanopore sequencer. Sequenced data were analyzed using web-based tools BugSeq and MicrobiomeAnalyst. Results: We found that certain bacterial families like Clostridia UCG 014, Cristensenellaceae, and Oscillospiraceae are higher in abundance, and Lachinospiracea, Coriobacteriaceae and genera associated with short-chain fatty acid production, Faecalibacterium, Fusicatenibacter, Roseburia and Blautia, are lower in abundance among PD cases when compared with the HC. Genus Akkermansia, Dialister, Bacteroides, and Lachnospiraceae NK4A136 group positively correlated with constipation in PD. Conclusion: Observations from this study support the other global research on the PD gut microbiome background and provide fresh insight into the gut microbial composition of PD patients from a south Indian population. We report a higher abundance of Clostridia UCG 014 group, previously not linked to PD.

Gut microbiome in the emergence of antibiotic-resistant bacterial pathogens.

The human gastrointestinal tract is home to a complex and dynamic community of microorganisms known as gut microbiota, which provide the host with important metabolic, signaling, and immunomodulatory functions. Both the commensal and pathogenic members of the gut microbiome serve as reservoirs of antimicrobial-resistance genes (ARG), which can cause potential health threats to the host and can transfer the ARGs to the susceptible microbes and into the environment. Antimicrobial resistance is becoming a major burden on human health and is widely recognized as a global challenge. The diversity and abundance of ARGs in the gut microbiome are variable and depend on the exposure to healthcare-associated antibiotics, usage of antibiotics in veterinary and agriculture, and the migration of the population. The transfer frequency of the ARGs through horizontal gene transfer (HGT) with the help of mobile genetic elements (MGEs) like plasmids, transposons, or phages is much higher among bacteria living in the GI tract compared to other microbial ecosystems. HGT in gut bacteria is facilitated through multiple gene transfer mechanisms, including transformation, conjugation, transduction, and vesicle fusion. It is the need of the hour to implement strict policies to limit indiscriminate antibiotic usage when needed. Developing rapid diagnostic tests for resistance determination and alternatives to antibiotics like vaccination, probiotics, and bacteriophage therapy should have the highest priority in the research and development sectors. Collective actions for sustainable development against resistant pathogens by promoting endogenous gut microbial growth and diversity through interdisciplinary research and findings are key to overcoming the current antimicrobial resistance crisis.

Gut microbiome dysbiosis in neonatal sepsis.

Sepsis is a highly heterogeneous, life-threatening organ dysfunction primarily caused by a dysregulated immune response to counter bacterial, viral, or fungal infections, resulting in haemodynamic changes and significant morbidity and mortality across all ages. In recent times, it has become one of the foremost causes of morbidity and mortality among newborns globally. The neonates, particularly the preterm neonates, due to their immature immune systems and non-canonical microbial community acquisition in the gastrointestinal tract and other body habitats, are adversely affected compared to the elderly with immunocompromised conditions. The neonates could acquire microbiota in utero or during delivery from the mother's genital tract or postnatally from contact with hospital personnel and the immediate hospital environment after the birth. Other factors that may enhance the risk include early colonization of microbiota by pathogens that trigger dysbiosis of the gut microbiome accompanied by a dysregulated immune response, organ dysfunction, and potential death. The sepsis-linked mortality could be prevented by timely diagnosis, selective antibiotic therapy, and supportive postnatal care. Infections due to antibiotic-resistant bacteria severely restrict possible therapeutic options, thus extending hospital stays. A comprehensive analysis of the infecting pathogens, cognate host responses, and the microbiota present would certainly help formulate appropriate interventions.