The Alpine ibex (Capra ibex) gut microbiome, seasonal dynamics, and potential application in lignocellulose bioconversion.

Aiming to shed light on the biology of wild ruminants, we investigated the gut microbiome seasonal dynamics of the Alpine ibex (Capra ibex) from the Central Italian Alps. Feces were collected in spring, summer, and autumn during non-invasive sampling campaigns. Samples were analyzed by 16S rRNA amplicon sequencing, shotgun metagenomics, as well as targeted and untargeted metabolomics. Our findings revealed season-specific compositional and functional profiles of the ibex gut microbiome that may allow the host to adapt to seasonal changes in available forage, by fine-tuning the holobiont catabolic layout to fully exploit the available food. Besides confirming the importance of the host-associated microbiome in providing the phenotypic plasticity needed to buffer dietary changes, we obtained species-level genome bins and identified minimal gut microbiome community modules of 11-14 interacting strains as a possible microbiome-based solution for the bioconversion of lignocellulose to high-value compounds, such as volatile fatty acids.

Interplay between WNT/PI3K-mTOR axis and the microbiota in APC-driven colorectal carcinogenesis: data from a pilot study and possible implications for CRC prevention.

BACKGROUND: Wnt/ß-catenin signalling impairment accounts for 85% of colorectal cancers (CRCs), including sporadic and familial adenomatous polyposis (FAP) settings. An altered PI3K/mTOR pathway and gut microbiota also contribute to CRC carcinogenesis. We studied the interplay between the two pathways and the microbiota composition within each step of CRC carcinogenesis. METHODS: Proteins and target genes of both pathways were analysed by RT-qPCR and IHC in tissues from healthy faecal immunochemical test positive (FIT+, n = 17), FAP (n = 17) and CRC (n = 15) subjects. CRC-related mutations were analysed through NGS and Sanger. Oral, faecal and mucosal microbiota was profiled by 16 S rRNA-sequencing. RESULTS: We found simultaneous hyperactivation of Wnt/ß-catenin and PI3K/mTOR pathways in FAP-lesions compared to CRCs. Wnt/ß-catenin molecular markers positively correlated with Clostridium_sensu_stricto_1 and negatively with Bacteroides in FAP faecal microbiota. Alistipes, Lachnospiraceae, and Ruminococcaceae were enriched in FAP stools and adenomas, the latter also showing an overabundance of Lachnoclostridium, which positively correlated with cMYC. In impaired-mTOR-mutated CRC tissues, p-S6R correlated with Fusobacterium and Dialister, the latter also confirmed in the faecal-ecosystem. CONCLUSIONS: Our study reveals an interplay between Wnt/ß-catenin and PI3K/mTOR, whose derangement correlates with specific microbiota signatures in FAP and CRC patients, and identifies new potential biomarkers and targets to improve CRC prevention, early adenoma detection and treatment.

Resistance to freezing conditions of endemic Antarctic polychaetes is enhanced by cryoprotective proteins produced by their microbiome.

The microbiome plays a key role in the health of all metazoans. Whether and how the microbiome favors the adaptation processes of organisms to extreme conditions, such as those of Antarctica, which are incompatible with most metazoans, is still unknown. We investigated the microbiome of three endemic and widespread species of Antarctic polychaetes: Leitoscoloplos geminus, Aphelochaeta palmeri, and Aglaophamus trissophyllus. We report here that these invertebrates contain a stable bacterial core dominated by Meiothermus and Anoxybacillus, equipped with a versatile genetic makeup and a unique portfolio of proteins useful for coping with extremely cold conditions as revealed by pangenomic and metaproteomic analyses. The close phylosymbiosis between Meiothermus and Anoxybacillus and these Antarctic polychaetes indicates a connection with their hosts that started in the past to support holobiont adaptation to the Antarctic Ocean. The wide suite of bacterial cryoprotective proteins found in Antarctic polychaetes may be useful for the development of nature-based biotechnological applications.

The gut microbiota in adults with chronic intestinal failure.

OBJECTIVE: Fecal microbiota was investigated in adult patients with chronic intestinal failure (CIF) due to short bowel syndrome (SBS) with jejunocolonic anastomosis (SBS-2). Few or no data are available on SBS with jejunostomy (SBS-1) and CIF due to intestinal dysmotility (DYS) or mucosal disease (MD). We profiled the fecal microbiota of various pathophysiological mechanisms of CIF. METHODS: Cross-sectional study on 61 adults with CIF (SBS-1 30, SBS-2 17, DYS 8, MD 6). Fecal samples were collected and profiled by 16S rRNA amplicon sequencing. Healthy controls (HC) were selected from pre-existing cohorts, matched with patients by sex and age. RESULTS: Compared to HC, SBS-1, SBS-2 and MD patients showed lower alpha diversity; no difference was found for DYS. In beta diversity analysis, SBS-1, SBS-2 and DYS groups segregated from HC and from each other. Taxonomically, the CIF groups differed from HC even at the phylum level. In particular, CIF patients' microbiota was dominated by Lactobacillaceae and Enterobacteriaceae, while depleted in typical health-associated taxa belonging to Lachnospiraceae and Ruminococcaceae. Notably, compositional peculiarities of the CIF groups emerged. Furthermore, in the SBS groups, the microbiota profile differed according to the amount of parenteral nutrition required and the duration of CIF. CONCLUSIONS: CIF patients showed marked intestinal dysbiosis with microbial signatures specific to the pathophysiological mechanism of CIF as well as to the severity and duration of SBS.

Gut microbiome dynamics and Enterobacterales infection in liver transplant recipients: A prospective observational study.

Background & Aims: The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT). Methods: A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG). Results: Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients. Conclusions: GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis. Impact and implications: Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.

The gut microbiome of Baka forager-horticulturalists from Cameroon is optimized for wild plant foods.

The human gut microbiome is losing biodiversity, due to the "microbiome modernization process" that occurs with urbanization. To keep track of it, here we applied shotgun metagenomics to the gut microbiome of the Baka, a group of forager-horticulturalists from Cameroon, who combine hunting and gathering with growing a few crops and working for neighboring Bantu-speaking farmers. We analyzed the gut microbiome of individuals with different access to and use of wild plant and processed foods, to explore the variation of their gut microbiome along the cline from hunter-gatherer to agricultural subsistence patterns. We found that 26 species-level genome bins from our cohort were pivotal for the degradation of the wild plant food substrates. These microbes include Old Friend species and are encoded for genes that are no longer present in industrialized gut microbiome. Our results highlight the potential relevance of these genes to human biology and health, in relation to lifestyle.

Dispersion of antimicrobial resistant bacteria in pig farms and in the surrounding environment.

BACKGROUND: Antimicrobial resistance has been identified as a major threat to global health. The pig food chain is considered an important source of antimicrobial resistance genes (ARGs). However, there is still a lack of knowledge on the dispersion of ARGs in pig production system, including the external environment. RESULTS: In the present study, we longitudinally followed one swine farm located in Italy from the weaning phase to the slaughterhouse to comprehensively assess the diversity of ARGs, their diffusion, and the bacteria associated with them. We obtained shotgun metagenomic sequences from 294 samples, including pig feces, farm environment, soil around the farm, wastewater, and slaughterhouse environment. We identified a total of 530 species-level genome bins (SGBs), which allowed us to assess the dispersion of microorganisms and their associated ARGs in the farm system. We identified 309 SGBs being shared between the animals gut microbiome, the internal and external farm environments. Specifically, these SGBs were characterized by a diverse and complex resistome, with ARGs active against 18 different classes of antibiotic compounds, well matching antibiotic use in the pig food chain in Europe. CONCLUSIONS: Collectively, our results highlight the urgency to implement more effective countermeasures to limit the dispersion of ARGs in the pig food systems and the relevance of metagenomics-based approaches to monitor the spread of ARGs for the safety of the farm working environment and the surrounding ecosystems.

Phosphorus mining from marine sediments adopting different carbon/nitrogen strategies driven by anaerobic reactors: The exploration of potential mechanism and microbial activities.

To investigate the possibility of phosphorus (P) recovery from marine sediment and explore the role of the carbon: nitrogen ratio in affecting the internal P release under anaerobic conditions, we experimented with the external addition of carbon (acetic acid and glucose) and ammonia nitrogen (NH4-N) to expose P release mechanisms. The 24-day anaerobic incubations were conducted with four different carbon: nitrogen dosing groups including no NH4-N addition and COD/N ratios of 100, 50, and 10. The P release showed that extra NH4-N loading significantly suppressed the decomposition of P (p < 0.05) from the marine sediment, the maximum P release was 4.07 mg/L and 7.14 mg/L in acetic acid- and glucose-fed systems, respectively, without extra NH4-N addition. Additionally, the results exhibited that the imbalance of carbon: nitrogen not only failed to induce the production of organic P mineralization enzyme (alkaline phosphatase) in the sediment but also suppressed its activity under anaerobic conditions. The highest enzyme activity was observed in the group without additional NH4-N dosage, with rates of 1046.4 mg/(kg∙h) in the acetic acid- and 967.8 mg/(kg∙h) in the glucose-fed system, respectively. Microbial data analysis indicated that a decrease in the abundance of P release-regulating bacteria, including polyphosphate-accumulating organisms (Rhodobacteraceae) and sulfate-reducing bacteria (Desulfosarcinaceae), was observed in the high NH4-N addition groups. The observed reduction in enzyme activity and suppression of microbial activity mentioned above could potentially account for the inhibited P decomposition in the presence of high NH4-N addition under anaerobic conditions. The produced P-enriched solution from the bioreactors may offer a promising source for future recovery endeavors.

Routes of dispersion of antibiotic resistance genes from the poultry farm system.

Poultry farms are hotspots for the development and spread of antibiotic resistance genes (ARGs), due to high stocking densities and extensive use of antibiotics, posing a threat of spread and contagion to workers and the external environment. Here, we applied shotgun metagenome sequencing to characterize the gut microbiome and resistome of poultry, workers and their households - also including microbiomes from the internal and external farm environment - in three different farms in Italy during a complete rearing cycle. Our results highlighted a relevant overlap among the microbiomes of poultry, workers, and their families (gut and skin), with clinically relevant ARGs and associated mobile elements shared in both poultry and human samples. On a finer scale, the reconstruction of species-level genome bins (SGBs) allowed us to delineate the dynamics of microorganism and ARGs dispersion from farm systems. We found the associations with worker microbiomes representing the main route of ARGs dispersion from poultry to human populations. Collectively, our findings clearly demonstrate the urgent need to implement more effective procedures to counteract ARGs dispersion from poultry food systems and the relevance of metagenomics-based metacommunity approaches to monitor the ARGs dispersion process for the safety of the working environment on farms.

From Whole Genome Shotgun Sequencing to Viral Community Profiling: The ViromeScan Tool.

ViromeScan is an innovative metagenomic analysis tool that allows characterizing the taxonomy of viral communities from raw data of metagenomics sequencing, efficiently denoising samples from reads of other microorganisms. This means that users can use the same shotgun metagenomic sequencing data to fully characterize complex microbial ecosystems, including bacteria and viruses. Here we describe the analysis procedure with some examples, illustrating the processes computed by ViromeScan from raw data to the final output.

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.

Bifidobacterium in anticancer immunochemotherapy: friend or foe?

The gut microbiome has received a crescendo of attention in recent years due to myriad influences on human pathophysiology, including cancer. Anticancer therapy research is constantly looking for new hints to improve response to therapy while reducing the risk of relapse. In this scenario, Bifidobacterium, which inhabits the gut microbial ecosystem (especially that of children) and is considered a health-associated microbe, has emerged as a key target to assist anticancer treatments for a better prognosis. However, some researchers have recently hypothesized an unfavorable role of Bifidobacterium spp. in anticancer immunochemotherapy, leading to some confusion in the field. This narrative review summarizes the current knowledge on the role of Bifidobacterium spp. in relation to anticancer treatments, discussing the pros and cons of its presence in the gut microbiome of cancer patients. The current intervention strategies based on the administration of probiotic strains of Bifidobacterium are then discussed. Finally, the need to conduct further studies, especially functional ones, is underlined to provide robust experimental evidence, especially on the underlying molecular mechanisms, and thus resolve the controversies on this microbe for the long-term success of immunochemotherapy.

Connect the dots: sketching out microbiome interactions through networking approaches.

Microbiome networking analysis has emerged as a powerful tool for studying the complex interactions among microorganisms in various ecological niches, including the human body and several environments. This analysis has been used extensively in both human and environmental studies, revealing key taxa and functional units peculiar to the ecosystem considered. In particular, it has been mainly used to investigate the effects of environmental stressors, such as pollution, climate change or therapies, on host-associated microbial communities and ecosystem function. In this review, we discuss the latest advances in microbiome networking analysis, including methods for constructing and analyzing microbiome networks, and provide a case study on how to use these tools. These analyses typically involve constructing a network that represents interactions among microbial taxa or functional units, such as genes or metabolic pathways. Such networks can be based on a variety of data sources, including 16S rRNA sequencing, metagenomic sequencing, and metabolomics data. Once constructed, these networks can be analyzed to identify key nodes or modules important for the stability and function of the microbiome. By providing insights into essential ecological features of microbial communities, microbiome networking analysis has the potential to transform our understanding of the microbial world and its impact on human health and the environment.

Microbiome variation at the clam-sediment interface may explain changes in local productivity of Chamelea gallina in the North Adriatic sea.

BACKGROUND: The clam Chamelea gallina is an ecologically and economically important marine species in the Northwestern Adriatic Sea, which currently suffers from occasional, and still unexplained, widespread mortality events. In order to provide some glimpses in this direction, this study explores the connections between microbiome variations at the clam-sediment interface and the nutritional status of clams collected at four Italian production sites along the Emilia Romagna coast, with different mortality incidence, higher in the Northern sites and lower in the Southern sites. RESULTS: According to our findings, each production site showed a peculiar microbiome arrangement at the clam-sediment interface, with features that clearly differentiate the Northern and Southern sites, with the latter also being associated with a better nutritional status of the animal. Interestingly, the C. gallina digestive gland microbiome from the Southern sites was enriched in some health-promoting microbiome components, capable of supplying the host with essential nutrients and defensive molecules. Furthermore, in experiments conducted under controlled conditions in aquaria, we provided preliminary evidence of the prebiotic action of sediments from the Southern sites, allowing to boost the acquisition of previously identified health-promoting components of the digestive gland microbiome by clams from the Northern sites. CONCLUSIONS: Taken together, our findings may help define innovative microbiome-based management strategies for the preservation of the productivity of C. gallina clams in the Adriatic Sea, through the identification and maintenance of a probiotic niche at the animal-sediment interface.

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.

Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as a predictor of mortality in children.

The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.

Gut, oral, and nasopharyngeal microbiota dynamics in the clinical course of hospitalized infants with respiratory syncytial virus bronchiolitis.

Introduction: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospitalization in infants worldwide. The nasopharyngeal microbiota has been suggested to play a role in influencing the clinical course of RSV bronchiolitis, and some evidence has been provided regarding oral and gut microbiota. However, most studies have focused on a single timepoint, and none has investigated all three ecosystems at once. Methods: Here, we simultaneously reconstructed the gut, oral and nasopharyngeal microbiota dynamics of 19 infants with RSV bronchiolitis in relation to the duration of hospitalization (more or less than 5 days). Fecal samples, oral swabs, and nasopharyngeal aspirates were collected at three timepoints (emergency room admission, discharge and six-month follow-up) and profiled by 16S rRNA amplicon sequencing. Results: Interestingly, all ecosystems underwent rearrangements over time but with distinct configurations depending on the clinical course of bronchiolitis. In particular, infants hospitalized for longer showed early and persistent signatures of unhealthy microbiota in all ecosystems, i.e., an increased representation of pathobionts and a depletion of typical age-predicted commensals. Discussion: Monitoring infant microbiota during RSV bronchiolitis and promptly reversing any dysbiotic features could be important for prognosis and long-term health.