Approximately 95% of Colorectal cancers (CRC) consist of adenocarcinomas originating from colonic Adenomatous polyps (AP). Increasing importance in CRC occurrence and progression has been attributed to the gut microbiota; however, a huge proportion of microorganisms inhabit the human digestive system. So, to comprehensively study the microbial spatial variations and their role in CRC progression, from AP to the different CRC phases, a holistic vision is imperative, including the simultaneous evaluation of multiple niches from the gastrointestinal system. Through an integrated approach, we identified potential microbial and metabolic biomarkers, able to discriminate human CRC from AP and/or also the different Tumor node metastasis (TNM) staging. In addition, as the microbiota contributes to the production of essential metabolic products detectable in fecal samples, we analysed and compared metabolites obtained from CRC and AP patients by using a Nuclear magnetic resonance (NMR) approach. In this observational study, saliva, tissue and stool samples from 61 patients, have been collected, including 46 CRC and 15 AP patients, age and sex-matched, undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, the microbiota in the three-district between CRC and AP patients has been characterized, as well as in different CRC TNM stages. Subsequently, proton NMR spectroscopy has been used in combination with multivariate and univariate statistical approaches, to define the fecal metabolic profile of a restricted group of CRC and AP patients. CRC patients display a different profile of tissue and fecal microbiota with respect to AP patients. Significant differences have been observed in CRC tissue microbial clades, with a rise of the Fusobacterium genus. In addition, significant taxa increase at the genus level has been observed in stool samples of CRC patients. Furthermore, Fusobacterium found in intestinal tissue has been positively correlated with fecal Parvimonas, for the first time. Moreover, as predicted by metagenomics pathway analysis, a significant increase of lactate (p=0.037) has been observed in the CRC fecal metabolic profiles, and positively correlated with Bifidobacterium (p=0.036). Finally, minor bacterial differences in CRC patients at stage T2 (TNM classification) have been detected, with a raise of the Spirochaetota phylum in CRC samples, with a slight increase of the Alphaproteobacteria class in fecal samples. Our results suggest the importance of microbiota communities and oncometabolites in CRC development. Further studies on CRC/AP management with a focus on CRC assessment are needed to investigate novel microbial-related diagnostic tools aimed to improve therapeutic interventions.

In this exploratory study, we investigate the variation in the facial skin microbiome architecture through aging and their functional association with host genetic factors in a cohort of healthy women, living in the same area and without cutaneous diseases. Notably, facial skin microbiota (SM) samples were collected from a cohort of 15 healthy Caucasian females, firstly divided into three age groups (younger women aged 20–35 years old; middle aged women of 36–52 years old; and older women aged 53–68 years old). Then, the recruited cohort was divided into two groups based on their facial hydration level (dry and normal skin). The facial SM revealed a different composition in the three analyzed aging groups and between normal and dry skins. The middle-aged women also revealed functional variations associated with collagen biosynthesis and oxidative stress damage repair. Otherwise, the association between selected host SNPs (single nucleotide polymorphisms) and the facial SM profile showed significant associations, suggesting a negative correlation with collagen metabolism and ROS damage protection. Finally, the composition and functionality of the facial SM seemed to affect the aging process through the two aging-correlated pathways of host ROS damage repair and collagen metabolism. Our exploratory data could be useful for future studies characterizing the structure, function, and dynamics of the SM in the aging process to design personalized therapeutic agents focusing on potential genomic targets, microbes, and their metabolites.

Objectives: In systemic sclerosis (SSc), gastrointestinal involvement is one of the earliest events. We compared the gut microbiota (GM), its short-chain fatty acids (SCFAs) and host-derived free fatty acids (FFAs) in patients with very early diagnosis of SSc (VEDOSS) and definite SSc. Methods: Stool samples of 26 patients with SSc, 18 patients with VEDOSS and 20 healthy controls (HC) were collected. The GM was assessed through 16S rRNA sequencing, while SCFAs and FFAs were assessed by gas chromatography-mass spectrometry. Results: In patients with VEDOSS, an increase in Bacteroidales and Oscillospirales orders and a decrease in Bacilli class, Blautia, Romboutsia, Streptococcus and Turicibacter genera was detected in comparison with HC. In patients with SSc, an elevated number of Acidaminococcaceae and Sutterellaceae families, along with a decrease of the Peptostreptococcaceae family and Anaerostipes, Blautia, Romboutsia and Turicibacter genera was found in comparison with HC. Patients with SSc and VEDOSS had a significantly lower butyrate and higher acetate with respect to HC. In VEDOSS, an increase in Oscillospiraceae family and Anaerostipes genus, and a decrease in Alphaproteobacteria class, and Lactobacillales order was identified with respect to SSc. Moreover, patients with VEDOSS exhibited higher acetate and lower valerate compared with definite SSc. Conclusion: A GM dysbiosis with depletion of beneficial anti-inflammatory bacteria (especially butyrate-producing) and a significant decrease in faecal butyrate was identified in patients with VEDOSS. This early GM imbalance may foster the growth of inflammatory microbes, worsening intestinal dysbiosis and inflammation in early SSc stages. The potential butyrate administration in early disease phases might be considered as a novel therapeutic approach to mitigate gastrointestinal discomfort and progression preserving patient’s quality of life.

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut–retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)—known for their anti-inflammatory properties—on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography–mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations—such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing—this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut–retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

Amyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons’ pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments. Graphical abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A genome-wide association study showed a correlation between ANCA-negative EGPA and variants of genes encoding proteins with intestinal barrier functions, suggesting that modifications of the mucosal layer and consequent gut dysbiosis might be involved in EGPA pathogenesis. Here, we characterized the gut microbiota (GM) composition and the intestinal immune response in a cohort of EGPA patients. Faeces from 29 patients and 9 unrelated healthy cohabitants were collected, and GM and derived metabolites’ composition were compared. Seven intestinal biopsies from EGPA patients with gastrointestinal manifestations were analysed to assess the T-cell distribution and its correlation with GM and EGPA clinical and laboratory features. No significant differences in GM composition, nor in the total amount of faecal metabolites, emerged between patients and controls. Nevertheless, differences in bacterial taxa abundances and compositional GM-derived metabolites profile were observed. Notably, an enrichment of potential pathobionts (Enterobacteriacee and Streptococcaceae) was found in EGPA, particularly in patients with active disease, while lower levels were found in patients on immunosuppression, compared with non-immunosuppressed ones. Significantly lower amounts of hexanoic acid were found in patients, compared to controls. The analysis of the immune response in the gut mucosa revealed a high frequency of IFN-γ/IL-17-producing T lymphocytes, and a positive correlation between EGPA disease activity and intestinal T-cell levels. Our data suggest that an enrichment in potential intestinal pathobionts might drive an imbalanced inflammatory response in EGPA.