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.

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.

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.

Several studies reported alterations of the human gut microbiota (GM) during COVID-19. To evaluate the potential role of the GM as an early predictor of COVID-19 at disease onset, we analyzed gut microbial samples of 315 COVID-19 patients that differed in disease severity. We observed significant variations in microbial diversity and composition associated with increasing disease severity, as the reduction of short-chain fatty acid producers such as Faecalibacterium and Ruminococcus , and the growth of pathobionts as Anaerococcus and Campylobacter . Notably, we developed a multi-class machine-learning classifier, specifically a convolutional neural network, which achieved an 81.5% accuracy rate in predicting COVID-19 severity based on GM composition at disease onset. This achievement highlights its potential as a valuable early biomarker during the first week of infection. These findings offer promising insights into the intricate relationship between GM and COVID-19, providing a potential tool for optimizing patient triage and streamlining healthcare during the pandemic. IMPORTANCE: Efficient patient triage for COVID-19 is vital to manage healthcare resources effectively. This study underscores the potential of gut microbiota (GM) composition as an early biomarker for COVID-19 severity. By analyzing GM samples from 315 patients, significant correlations between microbial diversity and disease severity were observed. Notably, a convolutional neural network classifier was developed, achieving an 81.5% accuracy in predicting disease severity based on GM composition at disease onset. These findings suggest that GM profiling could enhance early triage processes, offering a novel approach to optimizing patient management during the pandemic.

The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood. To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life. Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics. Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet. Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.

Background: Chronic neuropathic low back pain (LBP) is a prevalent health condition and difficult to treat. Conventional therapies often provide limited relief and raise safety concerns. Supplemental palmitoylethanolamide (PEA), an endogenous fatty acid amide with analgesic and anti-inflammatory properties, has shown benefits in neuropathic pain, but its application as a supportive strategy has been limited by poor oral bioavailability. Objectives: This study aimed to investigate a phospholipid-based palmitoylethanolamide formulation (PEA-PL, Cronilief™), developed using Phytosome™ delivery technology, with respect to solubility optimization, systemic exposure, and associated clinical effects in individuals with chronic neuropathic LBP. Methods: PEA-PL solubility was assessed in fasted-state simulated intestinal fluid and compared with unformulated PEA. Plasma PEA concentrations were evaluated in healthy volunteers after 2 weeks of supplementation with unformulated PEA (300 mg/day) or PEA-PL (300 or 600 mg/day). Clinical efficacy was assessed in a double-blind, placebo-controlled randomized, trial in which 120 adults with neuropathic LBP received PEA-PL 600 → 300 mg (n = 40), PEA-PL 450 mg (n = 40), or placebo (n = 40), daily for 8 weeks in addition to Standard of Care. Primary outcomes were effects on neuropathic pain (Douleur Neuropathique 4, DN4) and its intensity (Numeric Pain Rating Scale, NPRS). Secondary outcomes included effect on functional disability (Oswestry Disability Index, ODI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), quality of life (QoL) (SF-12), and concomitant analgesic use. Safety was monitored throughout the 8-week supplementation period. Results: PEA-PL increased PEA solubility approximately eight-fold and resulted in higher plasma PEA concentrations than unformulated PEA. Both PEA-PL regimens significantly improved pain, functional disability, sleep, and QoL outcomes versus placebo (all p < 0.0001), with greater effects for the 600 → 300 mg regimen. Analgesic discontinuation occurred more frequently in PEA-PL groups (65–70%). Supplementation was well tolerated. Conclusions: A phospholipid-based (Phytosome™) PEA formulation (Cronilief™) was developed and associated with optimized systemic exposure and clinically meaningful reductions in pain severity and functional disability in individuals with chronic neuropathic LBP.