Microbiota-gut-brain axis and ketogenic diet: how close are we to tackling epilepsy?

The microbiota-gut-brain axis refers to the intricate bidirectional communication between commensal microorganisms residing in the digestive tract and the central nervous system, along neuroendocrine, metabolic, immune, and inflammatory pathways. This axis has been suggested to play a role in several neurological disorders, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy, paving the way for microbiome-based intervention strategies for the mitigation and treatment of symptoms. Epilepsy is a multifaceted neurological condition affecting more than 50 million individuals worldwide, 30% of whom do not respond to conventional pharmacological therapies. Among the first-hand microbiota modulation strategies, nutritional interventions represent an easily applicable option in both clinical and home settings. In this narrative review, we summarize the mechanisms underlying the microbiota-gut-brain axis involvement in epilepsy, discuss the impact of antiepileptic drugs on the gut microbiome, and then the impact of a particular dietary pattern, the ketogenic diet, on the microbiota-gut-brain axis in epileptic patients. The investigation of the microbiota response to non-pharmacological therapies is an ever-expanding field with the potential to allow the design of increasingly accessible and successful intervention strategies.

Gut microbiota resilience and recovery after anticancer chemotherapy.

Although research on the role of the gut microbiota (GM) in human health has sharply increased in recent years, what a "healthy" gut microbiota is and how it responds to major stressors is still difficult to establish. In particular, anticancer chemotherapy is known to have a drastic impact on the microbiota structure, potentially hampering its recovery with serious long-term consequences for patients' health. However, the distinguishing features of gut microbiota recovery and non-recovery processes are not yet known. In this narrative review, we first investigated how gut microbiota layouts are affected by anticancer chemotherapy and identified potential gut microbial recovery signatures. Then, we discussed microbiome-based intervention strategies aimed at promoting resilience, i.e., the rapid and complete recovery of a healthy gut microbial network associated with a better prognosis after such high-impact pharmacological treatments.

A personalized diet intervention improves depression symptoms and changes microbiota and metabolite profiles among community-dwelling older adults.

Introduction: The impact of diet on mental well-being and gut microorganisms in humans is well recognized. However, research on the connections between food nutrients, gut microbiota, and mental health remains limited. To address this, the present study aimed to assess the effects of a personalized diet, based on individual needs and aligned with the Mediterranean diet principles, on depression symptoms, quality of life, nutritional intake, and gut microbiota changes among older adults living in the community. Methods: The intervention involved regular visits from a registered dietitian, who provided tailored dietary recommendations. During the 6-month study, participants completed questionnaires to evaluate their depression levels, quality of life, and dietary habits. Additionally, they provided stool samples for analysis of gut microbiota and metabolites. Results: The results demonstrated that the personalized dietary intervention reduced depression symptoms and improved the quality of life among older adults. Furthermore, significant changes in the intake of certain nutrients, such as folate, lutein, zeaxanthin, EPA, and DHA, were observed following the intervention. Moreover, the intervention was associated with increased diversity in the gut microbiome and reduced total short-chain fatty acids, the main metabolites produced by gut microorganisms. The study also revealed correlations between food nutrients, gut microbiota, and mental health parameters. Discussion: In conclusion, this research highlights the potential advantages of personalized dietary interventions in managing depression and enhancing overall well-being among older populations. It also sheds light on the role of gut microbiota and its metabolites in these effects. The findings offer valuable insights into the significance of nutrition and gut health for mental well-being in older adults.

Cooking, Digestion, and In Vitro Colonic Fermentation of Nigerian Wholegrains Affect Phenolic Acid Metabolism and Gut Microbiota Composition.

Wholegrains contain both fibre and phenolic acids (PAs), and their gastrointestinal modifications are critical for their bioavailability and bioactivity. We evaluated the modifications on the PA profile and gut microbiota composition of selected Nigerian wholegrains, following cooking and gastrointestinal digestion. Red fonio, red millet, red sorghum, and white corn were cooked, digested, and fermented using an in vitro colonic model. A total of 26 PA derivatives were quantified in soluble and bound fractions using Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) analysis. DNA samples were analysed using 16S rRNA amplicon sequencing to profile the microbiota composition. The results show that cooking and digestion significantly affected the levels of PAs in all grains (p ≤ 0.05) compared to raw grains. Colonic fermentation resulted in a peak of total soluble PAs at 4-6 h for red sorghum and white corn and at 24 h for red millet and red fonio. Enterobacteriaceae genera were the most abundant at 24 h in all grains studied. 3-hydroxybenzaldehyde correlated positively with the relative abundance of Dorea and the mucus-degrader bacteria Akkermansia (p ≤ 0.05), whereas hydroferulic acid and isoferulic acid levels correlated negatively with Oscillospira and Ruminococcus (p ≤ 0.05), respectively. Our data indicate that cooking, digestion, and colonic fermentation affect the release of bound PAs from wholegrains and, consequently, their metabolic conversion. Furthermore, PA fermentation in the gut is associated with potentially relevant changes in the microbiota. This in vitro study provides the basis for the design of an in vivo human intervention study that can confirm the trends herein observed but also assess the impact on health outcomes.

Early-life gut microbiota and neurodevelopment in preterm infants: a narrative review.

Infants born preterm are at a high risk of both gut microbiota (GM) dysbiosis and neurodevelopmental impairment. While the link between early dysbiosis and short-term clinical outcomes is well established, the relationship with long-term infant health has only recently gained interest. Notably, there is a significant overlap in the developmental windows of GM and the nervous system in early life. The connection between GM and neurodevelopment was first described in animal models, but over the last decade a growing body of research has also identified GM features as one of the potential mediators for human neurodevelopmental and neuropsychiatric disorders. In this narrative review, we provide an overview of the developing GM in early life and its prospective relationship with neurodevelopment, with a focus on preterm infants. Animal models have provided evidence for emerging pathways linking early-life GM with brain development. Furthermore, a relationship between both dynamic patterns and static features of the GM during preterm infants' early life and brain maturation, as well as neurodevelopmental outcomes in early childhood, was documented. Future human studies in larger cohorts, integrated with studies on animal models, may provide additional evidence and help to identify predictive biomarkers and potential therapeutic targets for healthy neurodevelopment in preterm infants.

Gut-derived metabolites mediating cognitive development in 5-year-old children: Early-life transplant in mice has lasting effects throughout adulthood.

The gut microbiota has been causally linked to cognitive development. We aimed to identify metabolites mediating its effect on cognitive development, and foods or nutrients related to most promising metabolites. Faeces from 5-year-old children (DORIAN-PISAC cohort, including 90 general population families with infants, 42/48 females/males, born in 2011-2014) were transplanted (FMT) into C57BL/6 germ-free mice. Children and recipient mice were stratified by cognitive phenotype, or based on protective metabolites. Food frequency questionnaires were obtained in children. Cognitive measurements in mice included five Y-maze tests until 23 weeks post-FMT, and (at 23 weeks) PET-CT for brain metabolism and radiodensity, and ultrasound-based carotid vascular indices. Children (faeces, urine) and mice (faeces, plasma) metabolome was measured by 1H NMR spectroscopy, and the faecal microbiota was profiled in mice by 16S rRNA amplicon sequencing. Cognitive scores of children and recipient mice were correlated. FMT-dependent modifications of brain metabolism were observed. Mice receiving FMT from high-cognitive or protective metabolite-enriched children developed superior cognitive-behavioural performance. A panel of metabolites, namely xanthine, hypoxanthine, formate, mannose, tyrosine, phenylalanine, glutamine, was found to mediate the gut-cognitive axis in donor children and recipient mice. Vascular indices partially explained the metabolite-to-phenotype relationships. Children's consumption of legumes, whole-milk yogurt and eggs, and intake of iron, zinc and vitamin D appeared to support protective gut metabolites. Overall, metabolites involved in inflammation, purine metabolism and neurotransmitter synthesis mediate the gut-cognitive axis, and holds promise for screening. The related dietary and nutritional findings offer leads to microbiota-targeted interventions for cognitive protection, with long-lasting effects.

Gut microbiota in relation to frailty and clinical outcomes.

PURPOSE OF REVIEW: The gut microbiota is involved in several aspects of host health and disease, but its role is far from fully understood. This review aims to unveil the role of our microbial community in relation to frailty and clinical outcomes. RECENT FINDINGS: Ageing, that is the continuous process of physiological changes that begin in early adulthood, is mainly driven by interactions between biotic and environmental factors, also involving the gut microbiota. Indeed, our gut microbial counterpart undergoes considerable compositional and functional changes across the lifespan, and ageing-related processes may be responsible for - and due to - its alterations during elderhood. In particular, a dysbiotic gut microbiota in the elderly population has been associated with the development and progression of several age-related disorders. SUMMARY: Here, we first provide an overview of the lifespan trajectory of the gut microbiota in both health and disease. Then, we specifically focus on the relationship between gut microbiota and frailty syndrome, that is one of the major age-related burdens. Finally, examples of microbiome-based precision interventions, mainly dietary, prebiotic and probiotic ones, are discussed as tools to ameliorate the symptoms of frailty and its overlapping conditions (e.g. sarcopenia), with the ultimate goal of actually contributing to healthy ageing and hopefully promoting longevity.

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

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.

Levofloxacin prophylaxis and parenteral nutrition have a detrimental effect on intestinal microbial networks in pediatric patients undergoing HSCT.

The gut microbiome (GM) has shown to influence hematopoietic stem cell transplantation (HSCT) outcome. Evidence on levofloxacin (LVX) prophylaxis usefulness before HSCT in pediatric patients is controversial and its impact on GM is poorly characterized. Post-HSCT parenteral nutrition (PN) is oftentimes the first-line nutritional support in the neutropenic phase, despite the emerging benefits of enteral nutrition (EN). In this exploratory work, we used a global-to-local networking approach to obtain a high-resolution longitudinal characterization of the GM in 30 pediatric HSCT patients receiving PN combined with LVX prophylaxis or PN alone or EN alone. By evaluating the network topology, we found that PN, especially preceded by LVX prophylaxis, resulted in a detrimental effect over the GM, with low modularity, poor cohesion, a shift in keystone species and the emergence of modules comprising several pathobionts, such as Klebsiella spp., [Ruminococcus] gnavus, Flavonifractor plautii and Enterococcus faecium. Our pilot findings on LVX prophylaxis and PN-related disruption of GM networks should be considered in patient management, to possibly facilitate prompt recovery/maintenance of a healthy and well-wired GM. However, the impact of LVX prophylaxis and nutritional support on short- to long-term post-HSCT clinical outcomes has yet to be elucidated.

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

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.

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

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.

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

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.

Bacterial colonization dynamics of different microplastic types in an anoxic salt marsh sediment and impact of adsorbed polychlorinated biphenyls on the plastisphere.

Plastic debris dispersed into the environment provide a substrate for microbial colonization, constituting a new human-made ecosystem called "plastisphere", and altering the microbial species distribution in aquatic, coastal and benthic ecosystems. The study aims at exploring the interaction among microplastics (MPs) made of different polymers, a persistent organic contaminant (polychlorinated biphenyls, PCBs), and the environmental microbial communities, in an anoxic marine sediment. Plastic pellets were incubated in the field in a salt marsh anoxic sediment, to observe the stages of plastisphere formation, by quantitative PCR and 16S rRNA gene sequencing, and PCB dechlorination activity on the MPs surface. Microbes from the sediment rapidly colonized the different microplastics types, with PVC recruiting a peculiar community enriched in sulfate-reducing bacteria. The composition of the plastisphere varied along the 1-year incubation possibly in response either to warmer temperatures in spring-summer or to microhabitat's changes due to the progressive plastic surface weathering. Even if PCB contaminated MPs were able to recruit potentially dehalogenating taxa, actual dechlorination was not detectable after 1 year. This suggests that the concentration of potentially dehalorespiring bacteria in the natural environment could be too low for the onset of the dechlorination process on MP-sorbed contaminants. Our study, which is among very few available longitudinally exploring the plastisphere composition in an anoxic sediment context, is the first exploring the fate and possible biodegradation of persistent organic pollutants sorbed on MPs reaching the seafloor.

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

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.

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

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.

Age-related diseases, therapies and gut microbiome: A new frontier for healthy aging.

The gut microbiome is undoubtedly a key modulator of human health, which can promote or impair homeostasis throughout life. This is even more relevant in old age, when there is a gradual loss of function in multiple organ systems, related to growth, metabolism, and immunity. Several studies have described changes in the gut microbiome across age groups up to the extreme limits of lifespan, including maladaptations that occur in the context of age-related conditions, such as frailty, neurodegenerative diseases, and cardiometabolic diseases. The gut microbiome can also interact bi-directionally with anti-age-related disease therapies, being affected and in turn influencing their efficacy. In this framework, the development of integrated microbiome-based intervention strategies, aimed at favoring a eubiotic configuration and trajectory, could therefore represent an innovative approach for the promotion of healthy aging and the achievement of longevity.

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

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.

Fecal Microbiota Monitoring in Elite Soccer Players Along the 2019-2020 Competitive Season.

Physical exercise affects the human gut microbiota, which in turn influences athletes' performance. The current understanding of how the microbiota of professional athletes changes along with different phases of training is sparse. We aim to characterize the fecal microbiota in elite soccer players along with different phases of a competitive season using 16 S rRNA gene sequencing. Fecal samples were collected after the summer off-season period, the pre-season retreat, the first half of the competitive season, and the 8 weeks of COVID-19 lockdown that interrupted the season 2019-2020. According to our results, the gut microbiota of professional athletes changes along with the phases of the season, characterized by different training, diet, nutritional surveillance, and environment sharing. Pre-season retreat, during which nutritional surveillance and exercise intensity were at their peak, caused a decrease in bacterial groups related to unhealthy lifestyle and an increase in health-promoting symbionts. The competitive season and forced interruption affected other features of the athletes' microbiota, i.e., bacterial groups that respond to dietary fiber load and stress levels. Our longitudinal study, focusing on one of the most followed sports worldwide, provides baseline data for future comparisons and microbiome-targeting interventions aimed at developing personalized training and nutrition plans for performance maximization.

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

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.