Showing papers by "Patrizia Brigidi published in 2022"

Gut microbiome–micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins?

Abstract: Micronutrients, namely, vitamins and minerals, are necessary for the proper functioning of the human body, and their deficiencies can have dramatic short‐ and long‐term health consequences. Among the underlying causes, certainly a reduced dietary intake and/or poor absorption in the gastrointestinal tract play a key role in decreasing their bioavailability. Recent evidence from clinical and in vivo studies suggests an increasingly important contribution from the gut microbiome. Commensal microorganisms can in fact regulate the levels of micronutrients, both by intervening in the biosynthetic processes and by modulating their absorption. This short narrative review addresses the pivotal role of the gut microbiome in influencing the bioavailability of vitamins (such as A, B, C, D, E, and K) and minerals (calcium, iron, zinc, magnesium, and phosphorous), as well as the impact of these micronutrients on microbiome composition and functionality. Personalized microbiome‐based intervention strategies could therefore constitute an innovative tool to counteract micronutrient deficiencies by modulating the gut microbiome toward an eubiotic configuration capable of satisfying the needs of our organism, while promoting general health.

Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review

Abstract: There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers.

Polyphenol and Tannin Nutraceuticals and Their Metabolites: How the Human Gut Microbiota Influences Their Properties

Abstract: Nutraceuticals have been receiving increasing attention in the last few years due to their potential role as adjuvants against non-communicable chronic diseases (cardiovascular disease, diabetes, cancer, etc.). However, a limited number of studies have been performed to evaluate the bioavailability of such compounds, and it is generally reported that a substantial elevation of their plasma concentration can only be achieved when they are consumed at pharmacological levels. Even so, positive effects have been reported associated with an average dietary consumption of several nutraceutical classes, meaning that the primary compound might not be solely responsible for all the biological effects. The in vivo activities of such biomolecules might be carried out by metabolites derived from gut microbiota fermentative transformation. This review discusses the structure and properties of phenolic nutraceuticals (i.e., polyphenols and tannins) and the putative role of the human gut microbiota in influencing the beneficial effects of such compounds.

The Core Human Microbiome: Does It Exist and How Can We Find It? A Critical Review of the Concept

Abstract: The core microbiome, which refers to a set of consistent microbial features across populations, is of major interest in microbiome research and has been addressed by numerous studies. Understanding the core microbiome can help identify elements that lead to dysbiosis, and lead to treatments for microbiome-related health states. However, defining the core microbiome is a complex task at several levels. In this review, we consider the current state of core human microbiome research. We consider the knowledge that has been gained, the factors limiting our ability to achieve a reliable description of the core human microbiome, and the fields most likely to improve that ability. DNA sequencing technologies and the methods for analyzing metagenomics and amplicon data will most likely facilitate higher accuracy and resolution in describing the microbiome. However, more effort should be invested in characterizing the microbiome’s interactions with its human host, including the immune system and nutrition. Other components of this holobiontic system should also be emphasized, such as fungi, protists, lower eukaryotes, viruses, and phages. Most importantly, a collaborative effort of experts in microbiology, nutrition, immunology, medicine, systems biology, bioinformatics, and machine learning is probably required to identify the traits of the core human microbiome.

Febrile Neutropenia Duration Is Associated with the Severity of Gut Microbiota Dysbiosis in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Abstract: Simple Summary Febrile neutropenia is a common complication in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation. Its genesis is often attributed to infections; however, a specific cause frequently cannot be defined. We hypothesize that the composition of the intestinal flora may contribute to the genesis of the neutropenic fever. We analyzed the microbial composition of stool samples from pediatric patients from three European centers and assessed the relationship with the duration of the fever during neutropenia. We found that a more stable composition of the microbiota during the transplantation course is associated with a shorter duration of fever. Moreover, patients with a higher duration of fever presented higher levels of Collinsella, Megasphaera, Prevotella, Roseburia, Eggerthella and Akkermansia in the stool. Abstract Febrile neutropenia (FN) is a common complication in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Frequently, a precise cause cannot be identified, and many factors can contribute to its genesis. Gut microbiota (GM) has been recently linked to many transplant-related complications, and may also play a role in the pathogenesis of FN. Here, we conducted a longitudinal study in pediatric patients receiving HSCT from three centers in Europe profiling their GM during the transplant course, particularly at FN onset. We found that a more stable GM configuration over time is associated with a shorter duration of fever. Moreover, patients with longer lasting fever exhibited higher pre-HSCT levels of Collinsella, Megasphaera, Prevotella and Roseburia and increased proportions of Eggerthella and Akkermansia at the engraftment. These results suggest a possible association of the GM with the genesis and course of FN. Data seem consistent with previous reports on the relationship of a so-called “healthy” GM and the reduction of transplant complications. To our knowledge, this is the first report in the pediatric HSCT setting. Future studies are warranted to define the underling biological mechanisms and possible clinical implications.

Oral Lactoferrin Supplementation during Induction Chemotherapy Promotes Gut Microbiome Eubiosis in Pediatric Patients with Hematologic Malignancies

Abstract: Induction chemotherapy is the first-line treatment for pediatric patients with hematologic malignancies. However, several complications may arise, mainly infections and febrile neutropenia, with a strong impact on patient morbidity and mortality. Such complications have been shown to be closely related to alterations of the gut microbiome (GM), making the design of strategies to foster its eubiosis of utmost clinical importance. Here, we evaluated the impact of oral supplementation of lactoferrin (LF), a glycoprotein endowed with anti-inflammatory, immunomodulatory and antimicrobial activities, on GM dynamics in pediatric oncohematologic patients during induction chemotherapy. Specifically, we conducted a double blind, placebo-controlled trial in which GM was profiled through 16S rRNA gene sequencing before and after two weeks of oral supplementation with LF or placebo. LF was safely administered with no adverse effects and promoted GM homeostasis by favoring the maintenance of diversity and preventing the bloom of pathobionts (e.g., Enterococcus). LF could, therefore, be a promising adjunct to current therapeutic strategies in these fragile individuals to reduce the risk of GM-related complications.

Host microbiomes in tumor precision medicine: how far are we?

Abstract: The human gut microbiome has received a crescendo of attention in recent years, due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.

Multi-omics gut microbiome signatures in obese women: role of diet and uncontrolled eating behavior

Abstract: Abstract Background Obesity and related co-morbidities represent a major health challenge nowadays, with a rapidly increasing incidence worldwide. The gut microbiome has recently emerged as a key modifier of human health that can affect the development and progression of obesity, largely due to its involvement in the regulation of food intake and metabolism. However, there are still few studies that have in-depth explored the functionality of the human gut microbiome in obesity and even fewer that have examined its relationship to eating behaviors. Methods In an attempt to advance our knowledge of the gut-microbiome-brain axis in the obese phenotype, we thoroughly characterized the gut microbiome signatures of obesity in a well-phenotyped Italian female cohort from the NeuroFAST and MyNewGut EU FP7 projects. Fecal samples were collected from 63 overweight/obese and 37 normal-weight women and analyzed via a multi-omics approach combining 16S rRNA amplicon sequencing, metagenomics, metatranscriptomics, and lipidomics. Associations with anthropometric, clinical, biochemical, and nutritional data were then sought, with particular attention to cognitive and behavioral domains of eating. Results We identified four compositional clusters of the gut microbiome in our cohort that, although not distinctly associated with weight status, correlated differently with eating habits and behaviors. These clusters also differed in functional features, i.e., transcriptional activity and fecal metabolites. In particular, obese women with uncontrolled eating behavior were mostly characterized by low-diversity microbial steady states, with few and poorly interconnected species (e.g., Ruminococcus torques and Bifidobacterium spp.), which exhibited low transcriptional activity, especially of genes involved in secondary bile acid biosynthesis and neuroendocrine signaling (i.e., production of neurotransmitters, indoles and ligands for cannabinoid receptors). Consistently, high amounts of primary bile acids as well as sterols were found in their feces. Conclusions By finding peculiar gut microbiome profiles associated with eating patterns, we laid the foundation for elucidating gut-brain axis communication in the obese phenotype. Subject to confirmation of the hypotheses herein generated, our work could help guide the design of microbiome-based precision interventions, aimed at rewiring microbial networks to support a healthy diet-microbiome-gut-brain axis, thus counteracting obesity and related complications.

A Pilot Study on Donor Human Milk Microbiota: A Comparison with Preterm Human Milk Microbiota and the Effect of Pasteurization

Abstract: Human milk (HM) is the best feeding option for preterm infants; however, when mother’s own milk (MOM) is not available, pasteurized donor human milk (DHM) is the best alternative. In this study, we profiled DHM microbiota (19 samples) using 16S rRNA amplicon sequencing and compared its compositional features with the MOM microbiota (14 samples) from mothers who delivered prematurely (PT-MOM). As a secondary study aim, we assessed the specific effect of pasteurization on the characteristics of the DHM microbiota. DHM showed significantly higher alpha diversity and significant segregation from PT-MOM. Compositionally, the PT-MOM microbiota had a significantly higher proportion of Staphylococcus than DHM, with Streptococcus tending to be and Pseudomonas being significantly overrepresented in DHM compared with the PT-MOM samples. Furthermore, pasteurization affected the HM microbiota structure, with a trend towards greater biodiversity and some compositional differences following pasteurization. This pilot study provided further evidence on the HM microbial ecosystem, demonstrating that the DHM microbiota differs from the PT-MOM microbiota, possibly due to inherent differences between HM donors and mothers delivering prematurely, and that pasteurization per se impacts the HM microbiota. Knowledge about HM microbiota needs to be acquired by investigating the effect of DHM processing to develop strategies aimed at improving DHM quality while guaranteeing its microbiological safety.

Make It Less difficile: Understanding Genetic Evolution and Global Spread of Clostridioides difficile

Abstract: Clostridioides difficile is an obligate anaerobic pathogen among the most common causes of healthcare-associated infections. It poses a global threat due to the clinical outcomes of infection and resistance to antibiotics recommended by international guidelines for its eradication. In particular, C. difficile infection can lead to fulminant colitis associated with shock, hypotension, megacolon, and, in severe cases, death. It is therefore of the utmost urgency to fully characterize this pathogen and better understand its spread, in order to reduce infection rates and improve therapy success. This review aims to provide a state-of-the-art overview of the genetic variation of C. difficile, with particular regard to pathogenic genes and the correlation with clinical issues of its infection. We also summarize the current typing techniques and, based on them, the global distribution of the most common ribotypes. Finally, we discuss genomic surveillance actions and new genetic engineering strategies as future perspectives to make it less difficile.

Wholegrain fermentation affects gut microbiota composition, phenolic acid metabolism and pancreatic beta cell function in a rodent model of type 2 diabetes

Abstract: The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes (T2D), but dietary modification of the microbiota may promote glycemic control. Using a rodent model of T2D and an in vitro gut model system, this study investigated whether differences in gut microbiota between control mice and mice fed a high-fat, high-fructose (HFHFr) diet influenced the production of phenolic acid metabolites following fermentation of wholegrain (WW) and control wheat (CW). In addition, the study assessed whether changes in metabolite profiles affected pancreatic beta cell function. Fecal samples from control or HFHFr-fed mice were fermented in vitro with 0.1% (w/v) WW or CW for 0, 6, and 24 h. Microbiota composition was determined by bacterial 16S rRNA sequencing and phenolic acid (PA) profiles by UPLC-MS/MS. Cell viability, apoptosis and insulin release from pancreatic MIN6 beta cells and primary mouse islets were assessed in response to fermentation supernatants and selected PAs. HFHFr mice exhibited an overall dysbiotic microbiota with an increase in abundance of proteobacterial taxa (particularly Oxalobacteraceae) and Lachnospiraceae, and a decrease in Lactobacillus. A trend toward restoration of diversity and compositional reorganization was observed following WW fermentation at 6 h, although after 24 h, the HFHFr microbiota was monodominated by Cupriavidus. In parallel, the PA profile was significantly altered in the HFHFr group compared to controls with decreased levels of 3-OH-benzoic acid, 4-OH-benzoic acid, isoferulic acid and ferulic acid at 6 h of WW fermentation. In pancreatic beta cells, exposure to pre-fermentation supernatants led to inhibition of insulin release, which was reversed over fermentation time. We conclude that HFHFr mice as a model of T2D are characterized by a dysbiotic microbiota, which is modulated by the in vitro fermentation of WW. The differences in microbiota composition have implications for PA profile dynamics and for the secretory capacity of pancreatic beta cells.

The Relationship between Gut Microbiota and Respiratory Tract Infections in Childhood: A Narrative Review

Abstract: Respiratory tract infections (RTIs) are common in childhood and represent one of the main causes of hospitalization in this population. In recent years, many studies have described the association between gut microbiota (GM) composition and RTIs in animal models. In particular, the “inter-talk” between GM and the immune system has recently been unveiled. However, the role of GM in human, and especially infantile, RTIs has not yet been fully established. In this narrative review we provide an up-to-date overview of the physiological pathways that explain how the GM shapes the immune system, potentially influencing the response to common childhood respiratory viral infections and compare studies analysing the relationship between GM composition and RTIs in children. Most studies provide evidence of GM dysbiosis, but it is not yet possible to identify a distinct bacterial signature associated with RTI predisposition. A better understanding of GM involvement in RTIs could lead to innovative integrated GM-based strategies for the prevention and treatment of RTIs in the paediatric population.

Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out

Abstract: Anticancer treatments have shown a variable therapeutic outcome that may be partly attributable to the activity of the gut microbiota on the pathology and/or therapies. In recent years, microbiota–drug interactions have been extensively investigated, but most of the underlying molecular mechanisms still remain unclear. In this review, we discuss the relationship between the gut microbiota and some of the most commonly used drugs in oncological diseases. Different strategies for manipulating the gut microbiota layout (i.e., prebiotics, probiotics, antibiotics, and fecal microbiota transplantation) are then explored in order to optimize clinical outcomes in cancer patients. Anticancer technologies that exploit tumor-associated bacteria to target tumors and biotransform drugs are also briefly discussed. In the field of pharmacomicrobiomics, multi-omics strategies coupled with machine and deep learning are urgently needed to bring to light the interaction among gut microbiota, drugs, and host for the development of truly personalized precision therapies.

Gut Microbiota and Fear Processing in Women Affected by Obesity: An Exploratory Pilot Study

Abstract: The microbiota–gut–brain axis extends beyond visceral perception, influencing higher-order brain structures, and ultimately psychological functions, such as fear processing. In this exploratory pilot study, we attempted to provide novel experimental evidence of a relationship between gut microbiota composition and diversity, and fear-processing in obesity, through a behavioral approach. Women affected by obesity were enrolled and profiled for gut microbiota, through 16S rRNA amplicon sequencing. Moreover, we tested their ability to recognize facial fearful expressions through an implicit-facial-emotion-recognition task. Finally, a traditional self-report questionnaire was used to assess their temperamental traits. The participants exhibited an unbalanced gut microbiota profile, along with impaired recognition of fearful expressions. Interestingly, dysbiosis was more severe in those participants with altered behavioral performance, with a decrease in typically health-associated microbes, and an increase in the potential pathobiont, Collinsella. Moreover, Collinsella was related to a lower expression of the persistence temperamental trait, while a higher expression of the harm-avoidance temperament, related to fear-driven anxiety symptoms, was linked to Lactobacillus. Once confirmed, our findings could pave the way for the design of innovative microbiome-based strategies for the treatment of psychological and emotional difficulties by mitigating obesity-related consequences and behaviors.

Cerrado and Pantanal fruit flours affect gut microbiota composition in healthy and post‐COVID‐19 individuals: an in vitro pilot fermentation study

Abstract: Summary Cerrado and Pantanal plants can provide fruits with high nutritional value and antioxidants. This study aims to evaluate four fruit flours (from jatobá pulp, cumbaru almond, bocaiuva pulp and bocaiuva almond) and their effects on the gut microbiota in healthy (HD) and post‐COVID‐19 individuals (PC). An in vitro batch system was carried out, the microbiota was analysed by 16S rRNA amplicon sequencing and the short‐chain fatty acids ratio was determined. Furthermore, the effect of jatobá pulp flour oil (JAO) on cell viability, oxidative stress and DNA damage was investigated in a myelo‐monocytic cell line. Beyond confirming a microbiota imbalance in PC, we identified flour‐specific effects: (i) reduction of Veillonellaceae with jatobá extract in PC samples; (ii) decrease in Akkermansia with jatoba and cumbaru flours; (iii) decreasing trend of Faecalibacterium and Ruminococcus with all flours tested, with the exception of the bocaiuva almond in HD samples for Ruminococcus and (iv) increase in Lactobacillus and Bifidobacterium in PC samples with bocaiuva almond flour. JAO displayed antioxidant properties protecting cells from daunorubicin‐induced cytotoxicity, oxidative stress and DNA damage. The promising microbiota‐modulating abilities of some flours and the chemopreventive effects of JAO deserve to be further explored in human intervention studies.

Pharmacomicrobiomics in Pediatric Oncology: The Complex Interplay between Commonly Used Drugs and Gut Microbiome

Abstract: The gut microbiome (GM) has emerged in the last few years as a main character in several diseases. In pediatric oncological patients, GM has a role in promoting the disease, modulating the effectiveness of therapies, and determining the clinical outcomes. The therapeutic course for most pediatric cancer influences the GM due to dietary modifications and several administrated drugs, including chemotherapies, antibiotics and immunosuppressants. Interestingly, increasing evidence is uncovering a role of the GM on drug pharmacokinetics and pharmacodynamics, defining a bidirectional relationship. Indeed, the pediatric setting presents some contrasts with respect to the adult, since the GM undergoes a constant multifactorial evolution during childhood following external stimuli (such as diet modification during weaning). In this review, we aim to summarize the available evidence of pharmacomicrobiomics in pediatric oncology.

Gut Microbiota Dysbiosis in Childhood Vasculitis: A Perspective Comparative Pilot Study

Abstract: Kawasaki disease (KD) and Henoch–Schönlein purpura (HSP) are the most frequent vasculitis in childhood. For both, a multifactorial mechanism has been hypothesised, with an abnormal immune response in genetically predisposed children. Gut microbiota (GM) alterations might trigger the hyperimmune reaction. Our aim was to explore the GM in KD and compare it with the GM of HSP and febrile children. Children diagnosed with KD, HSP and non-KD febrile illness (F) were enrolled. GM was profiled by 16S rRNA gene sequencing and compared with the profiles of healthy children from previous studies. We enrolled 13 KD, 10 HSP and 12 F children. Their GM significantly differed from controls, with an overall reduction in the relative abundance of beneficial taxa belonging to the Ruminococcaceae and Lachnospiraceae families. Potential KD and HSP signatures were identified, including smaller amounts of Dialister in the former, and Clostridium and Akkermansia in the latter. Notably, the GM structures of KD, HSP and F patients stratified by abdominal involvement, with more severe dysbiosis in those suffering from intestinal symptoms. This is the first study analysing GM in a mostly Caucasian cohort of KD and HSP children. Our data could open up new opportunities for childhood vasculitis treatment.