Stefania Pane

Background/Objectives: The gut microbiota (GM) is pivotal for immune regulation, metabolism, and neurodevelopment. Infants undergoing surgery for congenital gastrointestinal anomalies are especially prone to microbial imbalances, with a paucity of beneficial bacteria (e.g., Bifidobacteria and Bacteroides) and diminished short-chain fatty acid production. Dysbiosis has been associated with severe complications, including necrotizing enterocolitis, sepsis, and feeding intolerance. This narrative review aims to critically examine strategies for microbiota modulation in this high-risk cohort. Methods: An extensive literature analysis was performed to compare the evolution of GM in healthy neonates versus those requiring gastrointestinal surgery, synthetizing strategies to maintain eubiosis, such as early nutritional interventions—particularly the use of human milk—along with antibiotic management and supplementary treatments including probiotics, prebiotics, postbiotics, and lactoferrin. Emerging techniques in metagenomic and metabolomic analysis were also evaluated for their potential to elucidate microbial dynamics in these patients. Results: Neonates undergoing gastrointestinal surgery exhibit significant alterations in microbial communities, characterized by reduced levels of eubiotic bacteria and an overrepresentation of opportunistic pathogens. Early initiation of enteral feeding with human milk and careful antibiotic stewardship are linked to improved microbial balance. Adjunctive therapies, such as the administration of probiotics and lactoferrin, show potential in enhancing gut barrier function and immune modulation, although confirmation through larger-scale studies remains necessary. Conclusions: Modulating the GM emerges as a promising strategy to ameliorate outcome in neonates with congenital gastrointestinal surgical conditions. Future research should focus on the development of standardized therapeutic protocols and the execution of rigorous multicenter trials to validate the efficacy and safety of these interventions.

Cryptosporidium spp. are zoonotic protozoan parasites with a global prevalence, with both gastrointestinal and pulmonary involvement. Though symptoms can often be relatively mild, they can become severe and even fatal in children under five, the elderly, and in immunocompromised individuals, making cryptosporidiosis a leading cause of morbidity and mortality in fragile populations. Furthermore, there is an urgent clinical need for alternative therapies against cryptosporidiosis, as currently available FDA-approved treatments are ineffective in the immunocompromised. Recent evidence in animal models suggests that the gut microbiota (GM) can influence both host and parasite biology to influence the course of Cryptosporidium infection. Here, we present GM profiles in five cases of cryptosporidiosis, associated with varying underlying pathologies. We found that moderate–severe cryptosporidiosis was characterized by a reduction in alpha-diversity and an enrichment of Enterococcus spp., while decreases in Bifidobacterium, Gemmiger, and Blautia were detectable in the milder manifestations of the disease. Our results suggest that severe cryptosporidiosis is associated with a stronger change on the GM than is age or underlying pathology. Together with previously published studies in animal models, we believe that these results suggest that the GM could be a potential therapeutic target for human patients as well, particularly in the immunocompromised for whom anti-Cryptosporidium treatment remains largely ineffective.

Pneumonia caused by Pneumocystis jirovecii infection (PCP) is a potentially life-threatening illness, particularly affecting the immunocompromised. The past two decades have shown an increase in PCP incidence; however, the underlying factors that promote disease severity and fatality have yet to be fully elucidated. Recent evidence suggests that the microbiota of the respiratory tract may play a role in stimulating or repressing pulmonary inflammation, as well as the progression of both bacterial and viral pneumonia. Here, we employed 16S rRNA metataxonomic sequencing to profile the respiratory microbiota of patients with mild-moderate and severe PCP. Our results show that the upper and lower airways of PCP patients have bacterial profiles which have been associated with a pro-inflammatory response. Furthermore, we find that severe PCP is associated with lower bacterial diversity and an increase in Prevotella and a decrease in Neisseria. Functionally, severe PCP was associated with a decrease in metabolic pathways of molecules with anti-inflammatory and antimicrobial properties. To our knowledge, this is the first study showing an association of PCP severity with shifts in the respiratory microbiome and may provide some insight into which patients are more susceptible to the more severe manifestations of the disease.

Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as “CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis” (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor–receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child’s gut symptoms cleared, without CDI recurrence.

Ischemic stroke (IS) can be caused by perturbations of the gut–brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk factors and can influence the brain through the production of different metabolites, such as short-chain fatty acids (SCFAs), indole and derivatives. This study examines ecological changes in the GM and its metabolic activities after stroke. Fecal samples of 10 IS patients were compared to 21 healthy controls (CTRLs). GM ecological profiles were generated via 16S rRNA taxonomy as functional profiles using metabolomics analysis performed with a gas chromatograph coupled to a mass spectrometer (GC-MS). Additionally fecal zonulin, a marker of gut permeability, was measured using an enzyme-linked immuno assay (ELISA). Data were analyzed using univariate and multivariate statistical analyses and correlated with clinical features and biochemical variables using correlation and nonparametric tests. Metabolomic analyses, carried out on a subject subgroup, revealed a high concentration of fecal metabolites, such as SCFAs, in the GM of IS patients, which was corroborated by the enrichment of SCFA-producing bacterial genera such as Bacteroides, Christensellaceae, Alistipes and Akkermansia. Conversely, indole and 3-methyl indole (skatole) decreased compared to a subset of six CTRLs. This study illustrates how IS might affect the gut microbial milieu and may suggest potential microbial and metabolic biomarkers of IS. Expanded populations of Akkermansia and enrichment of acetic acid could be considered potential disease phenotype signatures.

Cryptosporidiosis is increasingly identified as a leading cause of childhood diarrhea and malnutrition in both low-income and high-income countries. The strong impact on public health in epidemic scenarios makes it increasingly essential to identify the sources of infection and understand the transmission routes in order to apply the right prevention or treatment protocols. The objective of this literature review was to present an overview of the current state of human cryptosporidiosis, reviewing risk factors, discussing advances in the drug treatment and epidemiology, and emphasizing the need to identify a government system for reporting diagnosed cases, hitherto undervalued.

A growing body of evidence shows that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, which reduces host damage. Herein, we discuss how diagnostic parasitology may contribute to designing clinical metagenomic pipelines and FMT programs, especially in pediatric subjects. The consequences of more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.

A growing body of evidences is showing that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, with reduction of host damage. Herein, we discuss how diagnostic parasitology may contribute to design clinical metagenomics pipelines and FMT programs, especially in pediatric subjects. The consequences of a more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.