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Organic acids (OA) and nature-identical compounds (NIC) such as monoterpenes and aldehydes are well-known growth and health promoters in terrestrial livestock while their application for fish production is recent and their mechanisms of action require further study. Hence, this study tested the increasing dietary level (D0, D250, D500, D1000; 0, 250, 500 and 1000 mg kg feed−1 respectively) of a microencapsulated blend containing citric and sorbic acid, thymol and vanillin over 82 days on rainbow trout to assess the effects on growth, feed utilization, intestine cytokine gene expression and gut microbiota (GM). Furthermore, the effects on intestinal cytokine gene expression and GM were also explored after one week at high water temperature (23 °C). OA and NIC improved specific growth rate (SGR) and feed conversion rate (FCR) during the second half (day 40–82) of the feeding trial, while at the end of the trial protein (PER) and lipid efficiency (LER) increased with increasing dietary level. GM diversity and composition and cytokine gene expression analysis showed no significant differences in fish fed with increasing doses of OA and NIC (82 days) demonstrating the absence of inflammatory activity in the intestinal mucosa. Although there were no statistical differences, GM structure showed a tendency in clustering D0 group separately from the other dietary groups and a trend towards reduction of Streptococcus spp. was observed in the D250 and D1000 groups. After exposure to high water temperature, lower GM diversity and increased gene expression of inflammatory intestinal cytokines were observed for both inclusions (D0 vs. D1000) compared to groups in standard condition. However, the gene up-regulation involved a limited number of cytokines showing the absence of a substantial inflammation process able to compromise the functional activity of the intestine. Despite further study should be conducted to fully clarify this mechanism, cytokines up-regulation seems to be concomitant to the reduction of the GM diversity and, particularly, to the reduction of specific lactic acid bacteria such as Leuconostoc. The application of the microencapsulate blend tested can be a useful strategy to improve growth and feed utilization in rainbow trout under normal temperature conditions. According to the results organic acids and nature-identical compounds did not revert the effects triggered by the increased temperature of water.

Simple Summary This pilot study on the trajectory of the gut microbiota (GM) in patients with epithelial ovarian cancer undergoing neoadjuvant and adjuvant chemotherapy highlighted peculiar dynamics associated with the therapeutic outcome. In particular, platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of lactate-producing microorganisms compared to those sensitive to platinum. These potential GM signatures of therapeutic failure are detectable within the first half of chemotherapy cycles, suggesting that early integrated treatments also aimed at modulating GM could influence therapeutic outcome. Further studies in larger cohorts combining multiple omics and possibly animal models are urgently needed for in-depth mechanistic understanding. Abstract Epithelial ovarian cancer (EOC) is one of the most lethal and silent gynecological tumors. Despite appropriate surgery and chemotherapy, relapse occurs in over half of patients with a poor prognosis. Recently, the gut microbiota (GM) was hypothesized to influence the efficacy of anticancer therapies, but no data are available in EOC. Here, by 16S rRNA gene sequencing and inferred metagenomics, we profiled the GM of EOC patients at diagnosis and reconstructed its trajectory along the course of neoadjuvant or adjuvant chemotherapy up to follow-up. Compared to healthy subjects, the GM of EOC patients appeared unbalanced and severely affected by chemotherapy. Strikingly, discriminating patterns were identified in relation to the therapeutic response. Platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability with loss of health-associated taxa and increased proportions of Coriobacteriaceae and Bifidobacterium. Notably, most of these microorganisms are lactate producers, suggesting increased lactate production as supported by inferred metagenomics. In contrast, the GM of platinum-sensitive patients appeared overall more diverse and stable and enriched in lactate utilizers from the Veillonellaceae family. In conclusion, we identified potential GM signatures of therapeutic outcome in EOC patients, which could open up new opportunities for cancer prognosis and treatment.

In Mediterranean aquaculture, significant advances have been made towards a reduction of marine-derived ingredients in aquafeed formulation, as well as in defining the effect on how environmental factors such as rearing density interact with fish health. Little research, however, has examined the interaction between rearing density and dietary composition on main key performance indicators, physiological processes and gut bacterial community. A study was undertaken, therefore to assess growth response, digestive enzyme activity, humoral immunity on skin mucus, plasma biochemistry and gut microbiota of gilthead sea bream (Sparus aurata, L. 1758) reared at high (HD, 36–44 kg m−3) and low (LD, 12–15 kg m−3) final stocking densities and fed high (FM30/FO15, 30% fishmeal FM, 15% fish oil, FO) and low (FM10/FO3; 10% FM and 3% FO) FM and FO levels. Isonitrogenous and isolipidic extruded diets were fed to triplicate fish groups (initial weight: 96.2 g) to overfeeding over 98 days. The densities tested had no major effects on overall growth and feed efficiency of sea bream reared at high or low FM and FO dietary level. However, HD seems to reduce feed intake compared to LD mainly in fish fed FM30/FO15. Results of digestive enzyme activity indicated a comparable digestive efficiency among rearing densities and within each dietary treatment even if intestinal brush border enzymes appeared to be more influenced by stocking density compared to gastric and pancreatic enzymes. Plasma parameters related to nutritional and physiological conditions were not affected by rearing densities under both nutritional conditions a similar observation was also achieved through the study of lysozyme, protease, antiprotease and total protein determination in skin mucus, however; in this case lysozyme was slightly reduced at HD. For the first time on this species, the effect of rearing density on gut bacterial community was studied. Different response in relation to dietary treatment under HD and LD were detected. Low FM-FO diet maintained steady the biodiversity of the gut bacterial community between LD and HD conditions while fish fed high FM-FO level showed a reduced biodiversity at HD. According to the results, it seems feasible to rear gilthead sea bream at the on-growing phase at a density up to 36–44 kg m−3 with low or high FM-FO diet without negatively affecting growth, feed efficiency, welfare condition and gut bacterial community. info:eu-repo/semantics/acceptedVersion

Multiple sclerosis (MS) is a neurodegenerative inflammatory condition mediated by autoreactive immune processes. Due to its potential to influence host immunity and gut-brain communication, the gut microbiota has been suggested to be involved in the onset and progression of MS. To date, there is no definitive cure for MS, and rehabilitation programs are of the utmost importance, especially in the later stages. However, only a few people generally participate due to poor support, knowledge, and motivation, and no information is available on gut microbiota changes. Herein we evaluated the potential of a brief high-impact multidimensional rehabilitation program (B-HIPE) in a leisure environment to affect the gut microbiota, mitigate MS symptoms and improve quality of life. B-HIPE resulted in modulation of the MS-typical dysbiosis, with reduced levels of pathobionts and the replenishment of beneficial short-chain fatty acid producers. This partial recovery of a eubiotic profile could help counteract the inflammatory tone typically observed in MS, as supported by reduced circulating lipopolysaccharide levels and decreased populations of pro-inflammatory lymphocytes. Improved physical performance and fatigue relief were also found. Our findings pave the way for integrating clinical practice with holistic approaches to mitigate MS symptoms and improve patients’ quality of life.

Fishmeal (FM) possesses one of the highest buffering capacities in comparison to most alternative vegetable aquafeed ingredients and its decreasing content in current formulations might affect the ideal gastrointestinal environment for digestive enzyme action and gut bacterial community of carnivorous fish species. A study was undertaken, therefore, to assess growth response, gastrointestinal pH, digestive enzyme activity and gut bacterial community of European sea bass (Dicentrarchus labrax L.) juveniles fed low FM diets (10% FM) with or without a feed buffering additive, calcium carbonate (FM10 + B and FM10, respectively) in comparison to a standard FM diet (20% FM, FM20). Three isonitrogenous and isolipidic extruded diets were fed to triplicate fish groups of 80 individuals (initial weight: 23 g) to overfeeding over 64 days. No significant differences due to low FM dietary levels were observed in final body weight, specific growth rate, feed intake, feed and protein efficiency. Low FM diet did not affect gastrointestinal pH in the stomach, anterior intestine, mid-intestine and hindgut at 0, 4, 8 and 12 hours post meal (hpm) while the inclusion of calcium carbonate in low FM diet seems to slightly increase the pH in the hindgut at 12 hpm. The absence of significant differences of pepsin, chymotrypsin, amylase and lipase activity suggests a comparable digestive efficiency among treatments although trypsin activity was slightly reduced in low FM diets after 4 hpm. Decreasing FM content seems to exert an effect on the overall gut bacterial community analysed by next-generation sequencing even if no significant effects on specific bacterial component were detected. The gut bacterial community in all the treatments was particularly rich in lactic acid bacteria such as Lactobacillus spp. which may provide important beneficial functions for the host and be associated with a healthy intestinal epithelium. According to the results, increasing the feed buffering capacity does not seem to improve digestive conditions while it is feasible to include 10% FM dietary level in practical formulation for European sea bass juveniles without negatively affecting growth, feed efficiency and digestive luminal conditions. info:eu-repo/semantics/publishedVersion

A 121-day feeding trial was undertaken to test the effects of two dietary lipid levels (16 and 21% L16, L21) in triplicated gilthead sea bream groups (initial weight: 67.5 g) reared at two different water temperatures (high, H 23°C and low, L 17°C) in the same recirculation system but exposed to a switch in temperature after 58 days. Fish kept at H were transferred to L (HL transition, autumn shift), and the fish kept at L were exposed to H (LH transition, summer shift), while continuing to receive the same diet to apparent satiation in each group. At the end of the trial, no significant diet effect on specific growth rate (SGR), feed intake (FI), and feed conversion rate (FCR) were detected in fish exposed to HL transition compared with those exposed to LH transition, while gross lipid efficiency (GLE) and lipid efficiency ratio (LER) were higher in L16. After temperature changes, L16 displayed higher SGR, FI, GLE, and LER, while mesenteric fat index was reduced. After temperature changes, the combined effects of low lipid diet and low temperature conditions resulted in higher pepsin activity, while trypsin, chymotrypsin, and lipase activities were generally higher at high lipid content. The combined effect of diet and temperature did not alter the metabolic plasma profile, except for the observed final higher aspartate aminotransferase (AST) and alkaline phosphatase (ALP) values when combining high dietary lipid (L21) and temperature changes. Different diets showed a significantly different gut microbiome layout, only at high temperature with L16 diet resulting in a higher load of Lactobacillus. On the contrary, no dietary impact on ecosystem diversity was observed, independently from the temperature. In addition, L16 diet in the HL transition favored an increase in Weissella and Bradyrhizobium genera in the gut microbiome, while in the final condition of LH transition, L21 diet favored a significant increase in Streptococcus and Bacillus. According to the results, the utilization of 16% dietary lipid levels in gilthead sea bream should be preferred during seasonal temperature changes in order to optimize feed utilization and gut health., This research was undertaken under the MedAID (Mediterranean Aquaculture Integrated Development) project, which has received funding from the European Union’s Horizon 2020 Research and Innovation Programme, Call H2020-SFS-23-2016, Grant agreement no. 727315 (http://www.medaid-h2020.eu/). MY and NG received support from the Spanish Ministry of Science, Innovation and Universities (MCIU), the State Research Agency (AEI), the European Regional Development Fund (FEDER/ERDF), and project Thermodigest (RTI2018-096134-B-I00) granted to MY.

The SARS-CoV-2-associated COVID-19 pandemic has shaken the global healthcare system. Although the best-known symptoms are dry cough and pneumonia, viral RNA has been detected in the stool and about half of COVID-19 patients exhibit gastrointestinal upset. In this scenario, special attention is being paid to the possible role of the gut microbiota (GM). Fecal samples from 69 COVID-19 patients from three different hospitals of Bologna (Italy) were analyzed by 16S rRNA gene-based sequencing. The GM profile was compared with the publicly available one of healthy age- and gender-matched Italians, as well as with that of other critically ill non-COVID-19 patients. The GM of COVID-19 patients appeared severely dysbiotic, with reduced diversity, loss of health-associated microorganisms and enrichment of potential pathogens, particularly Enterococcus. This genus was far overrepresented in patients developing bloodstream infections (BSI) and admitted to the intensive care unit, while almost absent in other critically ill non-COVID-19 patients. Interestingly, the percentage of patients with BSI due to Enterococcus spp. was significantly higher during the COVID-19 pandemic than in the previous 3 years. Monitoring the GM of critically ill COVID-19 patients could help clinical management, by predicting the onset of medical complications such as difficult-to-treat secondary infections.

Diet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with ≥ 1 risk factors for MS, of whom 33 consumed SA-derived fresh foods and 27 received probiotics over 30 days, with a 15-day follow-up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters, previous dietary habits were investigated through a validated food-frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA-based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely favorable, effect, although one out of three subjects no longer suffered from MS. These findings suggest that improved dietary patterns can modulate the host microbiota and metabolome, counteracting the risk of developing MS.

Hepatic sinusoidal obstruction syndrome (SOS/VOD) represents a dramatic complication of hematopoietic stem cell transplantation (HSCT), particularly in children. Recent evidence has suggested a role for the gut microbiome (GM) in the context of HSCT and its related complications, but no data are available on the relationship between GM and SOS/VOD. Here, we conducted a retrospective case–control study in allo-HSCT pediatric patients developing or not SOS/VOD and profiled their GM over time, from before the transplant up to 72 days after. A rich and diverse GM before HSCT was found to be associated with a reduced likelihood of developing SOS/VOD. Furthermore, prior to transplant, patients not developing SOS/VOD showed an enrichment in some typically health-associated commensals, such as Bacteroides, Ruminococcaceae and Lachnospiraceae. Their levels remained overall higher until post-transplant. This high-diversity configuration resembles that described in other studies for other HSCT-related complications, including graft-versus-host disease, potentially representing a common protective GM feature against HSCT complications.

Several studies showed that D-Limonene can improve metabolic parameters of obese mice via various mechanisms, including intestinal microbiota modulation. Nevertheless, its effective doses often overcome the acceptable daily intake, rising concerns about toxicity. In this study we administered to C57BL/6 mice for 84 days a food supplement based on D-Limonene, adsorbed on dietary fibers (FLS), not able to reach the bloodstream, to counteract the metabolic effects of a high-fat diet (HFD). Results showed that daily administration of D-Limonene (30 and 60 mg/kg body weight) for 84 days decreased the weight gain of HFD mice. After 84 days we observed a statistically significant difference in weight gain in the group of mice receiving the higher dose of FLS compared to HFD mice (35.24 ± 4.56 g vs. 40.79 ± 3.28 g, p &lt, 0.05). Moreover, FLS at both doses tested was capable of lowering triglyceridemia and also fasting glycemia at the higher dose. Some insights on the relevant fatty acid changes in hepatic tissues were obtained, highlighting the increased polyunsaturated fatty acid (PUFA) levels even at the lowest dose. FLS was also able to positively modulate the gut microbiota and prevent HFD-associated liver steatosis in a dose-dependent manner. These results demonstrate that FLS at these doses can be considered non-toxic and could be an effective tool to counteract diet-induced obesity and ameliorate metabolic profile in mice.

After spinal cord injury (SCI), patients face many physical and psychological issues including intestinal dysfunction and comorbidities, strongly affecting quality of life. The gut microbiota has recently been suggested to influence the course of the disease in these patients. However, to date only two studies have profiled the gut microbiota in SCI patients, months after a traumatic injury. Here we characterized the gut microbiota in a large Italian SCI population, within a short time from a not only traumatic injury. Feces were collected within the first week at the rehabilitation center (no later than 60 days after SCI), and profiled by 16S rRNA gene-based next-generation sequencing. Microbial profiles were compared to those publicly available of healthy age- and gender-matched Italians, and correlated to patient metadata, including type of SCI, spinal unit location, nutrition and concomitant antibiotic therapies. The gut microbiota of SCI patients shows distinct dysbiotic signatures, i.e. increase in potentially pathogenic, pro-inflammatory and mucus-degrading bacteria, and depletion of short-chain fatty acid producers. While robust to most host variables, such dysbiosis varies by lesion level and completeness, with the most neurologically impaired patients showing an even more unbalanced microbial profile. The SCI-related gut microbiome dysbiosis is very likely secondary to injury and closely related to the degree of completeness and severity of the lesion, regardless of etiology and time interval. This microbial layout could variously contribute to increased gut permeability and inflammation, potentially predisposing patients to the onset of severe comorbidities.

Dog evolution has long been debated, particularly with regards to the origin of domestication and its effects on the genome, but little is known about the role of the gut microbiome during the recent canine evolutionary history. We sequenced the metagenome of 13 canine coprolites dated ca. 3,600-3,450 y ago from the Bronze Age archaeological site of Solarolo (Italy), which housed a complex farming community. The microbiome structure of Solarolo dogs revealed continuity with that of modern dogs, but it also shared some features with the wild wolf microbiome, as a kind of transitional state between them. The dietary niche, as also inferred from the microbiome composition, was omnivorous, with evidence of consumption of starchy agricultural foods. Interestingly, the microbiome from Solarolo dogs was particularly enriched in sequences encoding alpha-amylases and complemented a low copy number of the host amylase (AMY2B) gene. These findings suggest that Neolithic dogs could have responded to the transition to a starch-rich diet by expanding microbial functionalities devoted to starch catabolism. Such a microbiome adaptive mechanism would have compensated for delayed host response to the new primarily abundant plant food resources, available from companionship with Bronze Age agriculturalists.

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray&ndash, Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.

A 71-day study was conducted to explore the effect of increasing dietary levels (0, 250, 500, 1000 mg kg feed−1; D0, D250, D500 and D1000, respectively) of a blend of microencapsulated organic acids (OA, specifically citric and sorbic acid) and nature identical compounds (NIC, specifically thymol and vanillin), on growth, intestinal immune parameters and gut microbiota (GM) of European sea bass juveniles reared under normal and subsequently suboptimal environmental conditions (high temperature, 30.0 ± 0.4 °C and low oxygen, 4.6 ± 0.6 mg L−1). OA and NIC did not promote growth, feed utilisation and feed intake at the inclusion tested but induced a significantly upregulation of IL-8, IL-10 and TGFβ. GM analyzed by next-generation sequencing showed that OA and NIC were able to exert prebiotic properties stimulating the development of beneficial bacteria taxa such as Lactobacillus, Leuconostoc, and Bacillus sp. Picrust analyses displayed a significant potential functional reconfiguration of GM promoting a decrease in inflammation-promoting and homeostatic functions at increasing OA and NIC administration. For the first time on this species the exposure to suboptimal rearing conditions was able to modify GM structure reducing LAB and increasing Proteobacteria, findings which were consistent with the inflammatory process observed at mRNA level.

The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging., The gut microbiome of long-lived people display an increasing abundance of subdominant species, as well as a rearrangement in health-associated bacteria, but less is known about microbiome functions. In order to disentangle the contribution of the gut microbiome to the complex trait of human longevity, we here describe the metagenomic change of the human gut microbiome along with aging in subjects with up to extreme longevity, including centenarians (aged 99 to 104 years) and semisupercentenarians (aged 105 to 109 years), i.e., demographically very uncommon subjects who reach the extreme limit of the human life span. According to our findings, the gut microbiome of centenarians and semisupercentenarians is more suited for xenobiotic degradation and shows a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Collectively, our data go beyond the relationship between intestinal bacteria and physiological changes that occur with aging by detailing the shifts in the potential metagenomic functions of the gut microbiome of centenarians and semisupercentenarians as a response to progressive dietary and lifestyle modifications. IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging.

Nutritional iron deficiency (ID) causes not only anemia but also malfunction of the entire human organism. Recently, a role of the gut microbiota has been hypothesized, but limited data are available especially in infants. Here, we performed a pilot study to explore the gut microbiota in 10 patients with iron deficiency anemia (IDA) and 10 healthy controls aged 6–34 months. Fresh stool samples were collected from diapers, and the fecal microbiota was profiled by next-generation sequencing of the V3–V4 hypervariable region of the 16S rRNA gene. Except for diet diversity, the breastfeeding status at the enrollment, the exclusive breastfeeding duration, and the introduction of complementary foods did not differ between groups. Distinct microbial signatures were found in IDA patients, with increased relative abundance of Enterobacteriaceae (mean relative abundance, patients vs. controls, 4.4% vs. 3.0%) and Veillonellaceae (13.7% vs. 3.6%), and reduced abundance of Coriobacteriaceae (3.5% vs. 8.8%) compared to healthy controls. A decreased Bifidobacteriaceae/Enterobacteriaceae ratio was observed in IDA patients. Notwithstanding the low sample size, our data highlight microbiota dysbalance in IDA worth for further investigations, aimed at unraveling the ID impact on the microbiome trajectory in early life, and the possible long-term consequences.

Hematopoietic stem cell transplantation (HSCT) is the first-line immunotherapy to treat several hematologic disorders, although it can be associated with many complications reducing the survival rate, such as acute graft-versus-host disease (aGvHD) and infections. Given the fundamental role of the gut microbiome (GM) for host health, it is not surprising that a suboptimal path of GM recovery following HSCT may compromise immune homeostasis and/or increase the risk of opportunistic infections, with an ultimate impact in terms of aGvHD onset. Traditionally, the first nutritional approach in post-HSCT patients is parenteral nutrition (PN), which is associated with several clinical adverse effects, supporting enteral nutrition (EN) as a preferential alternative. The aim of the study was to evaluate the impact of EN vs. PN on the trajectory of compositional and functional GM recovery in pediatric patients undergoing HSCT. The GM structure and short-chain fatty acid (SCFA) production profiles were analyzed longitudinally in twenty pediatric patients receiving HSCT&mdash, of which, ten were fed post-transplant with EN and ten with total PN. According to our findings, we observed the prompt recovery of a structural and functional eubiotic GM layout post-HSCT only in EN subjects, thus possibly reducing the risk of systemic infections and GvHD onset.

Longevity has been described as the result of a complex combination of variables, hailing from genetics, lifestyle and environment. In this context, the intestinal microbiome has been proposed as a possible mediator of healthy aging that preserves host-environment homeostasis by counteracting inflammaging, intestinal permeability, and deterioration of cognitive and bone health. Correlations have been previously found between age-related gut microbiota dysbioses and levels of pro-inflammatory cytokines, hospitalization, poor diet and frailty in the elderly. More recently, the longest human gut microbiota trajectory along aging has been built, by comparing the fecal bacterial taxa from healthy adults and older individuals, also including semi-supercentenarians, i.e. people aged 105 or older. However, the functional changes that occur in the gut microbiome along with age are still largely unexplored. In an attempt to provide some glimpses in this direction and advance our knowledge on whether and how the gut microbiome may support the maintenance of health in extreme aging, here we characterized the fecal microbiome of 62 individuals, with age ranging from 22 to 105 years, by shotgun metagenomics. According to our findings, aging is characterized by an increased number of genes involved in xenobiotics degradation, as well as by rearrangements in metabolic pathways related to carbohydrate, amino acid and lipid metabolism. These microbiome features are even more boosted in semi-supercentenarians, probably representing the result of a life-long adaptive response to progressive changes in diet and lifestyle.

International audience; Several commensal and pathogenic Gram-negative bacteria produce DNA-damaging toxins that are considered bona fide carcinogenic agents. The microbiota of colorectal cancer (CRC) patients is enriched in genotoxin-producing bacteria, but their role in the pathogenesis of CRC is poorly understood. The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in the majority of sporadic CRCs. We investigated whether the loss of APC alters the response of colonic epithelial cells to infection by Salmonella enterica, the only genotoxin-producing bacterium associated with cancer in humans. Using 2D and organotypic 3D cultures, we found that APC deficiency was associated with sustained activation of the DNA damage response, reduced capacity to repair different types of damage, including DNA breaks and oxidative damage, and failure to induce cell cycle arrest. The reduced DNA repair capacity and inability to activate adequate checkpoint responses was associated with increased genomic instability in APC-deficient cells exposed to the genotoxic bacterium. Inhibition of the checkpoint response was dependent on activation of the phosphatidylinositol 3-kinase pathway. These findings highlight the synergistic effect of the loss of APC and infection with genotoxin-producing bacteria in promoting a microenvironment conducive to malignant transformation.

Accompanying human beings since the Paleolithic period, dogs has been recently regarded as a reliable model for the study of the gut microbiome connections with health and disease. In order to provide some glimpses on the connections between the gut microbiome layout and host behavior, we profiled the phylogenetic composition and structure of the canine gut microbiome of dogs with aggressive (n = 11), phobic (n = 13) and normal behavior (n = 18). Hormones’ determination was made through Radio Immuno-Assay (RIA), and next generation sequencing of the V3–V4 gene region of the bacterial 16S rRNA was employed to determine gut microbiome composition. Our results did not evidence any significant differences of hormonal levels between the three groups. According to our findings, aggressive behavioral disorder was found to be characterized by a peculiar gut microbiome structure, with high biodiversity and enrichment in generally subdominant bacterial genera (i.e. Catenibacterium and Megamonas). On the other hand, phobic dogs were enriched in Lactobacillus, a bacterial genus with known probiotic and psychobiotic properties. Although further studies are needed to validate our findings, our work supports the intriguing opportunity that different behavioral phenotypes in dogs may be associated with peculiar gut microbiome layouts, suggesting possible connections between the gut microbiome and the central nervous system and indicating the possible adoption of probiotic interventions aimed at restoring a balanced host-symbiont interplay for mitigating behavioral disorders., Biological sciences; Microbiology; Endocrinology; Veterinary medicine; Animal behavior; Microbiome, Behavioral disorders, Aggressive dogs, Phobic dogs, Hormones

The loggerhead sea turtle (Caretta caretta) is the most widespread sea turtle species in the Mediterranean Sea and a relevant pollution 'flagship species'. Here, we profiled the faecal microbiota from 29 C. caretta from a rescue centre, and explored the impact of several variables linked to both the animal itself and the environment (i.e., tank water ecosystem). We show that loggerhead turtles share more gut microbiota features with carnivorous marine mammals, than with phylogenetically close, but herbivorous, turtles, as a confirmation of the gut microbiota adaptive function to diet and environment. We also highlight a relation between the microbiota composition and the size (and consequently the age) of the turtles. Finally, we point out that the gut microbiota of sea turtles shows unexpectedly low exchange of microbes with the aquatic environment and is resilient to the stress induced by short-time captivity.