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The gastro-intestinal tract is an extensive organ involved in several activities, with a crucial role in immunity. Billions of commensal and transient microorganisms, known as the gut microbiota, and potential pathogens, which are constantly stimulating intestinal immunity, colonize the intestinal epithelial surface. The gut microbiota may be regarded as analogous to a solid organ with multiple different functions. In the last decade, many studies have demonstrated that intestinal bacteria can be a decisive factor in the health-disease balance of the intestine, and they can also be responsible for illnesses in other locations. For this reason, fecal microbiota transplantation (FMT) represents an important therapeutic option for infections and hold promise for different clinical conditions, such as multiple sclerosis, autism, obesity, and other systemic diseases. FMT consists of the infusion of a fecal suspension from a healthy donor to a recipient in order to restore gut flora alterations. Similar to the gut, the female reproductive tract is an example of a very complex biological ecosystem. Recent studies indicate a possible relationship between the gut and female tract microbiota, associating specific intestinal bacteria patterns with genital female diseases, such as polycystic ovary syndrome (PCOS), endometriosis and bacterial vaginosis (BV). FMT could represent a potential innovative treatment option in this field.

Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea. Tyrosine kinase inhibitors (TKIs) have improved the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC), however TKI-related diarrhoea is a common and serious adverse effect. Here the authors show in a randomized clinical trial that faecal microbiota transplantation from healthy donors can improve TKI-induced diarrhoea in patients with mRCC.

Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT ( P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria ) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols. Coupling microbial metagenomics with machine learning enables prediction of donor strain engraftment after fecal microbiota transplantation (FMT) for a range of diseases, and may help tailor design of FMT to optimize microbial engraftment and achieve clinical outcomes.

Preliminary studies suggested a possible correlation of microbiota with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), where the need for tools to ameliorate its poor prognosis is mandatory. We explored the potential signature of esophageal microbiota and its predicted functional profile along the continuous spectrum from BE to EAC. We analyzed through 16S-based amplicon sequencing the mucosal microbiota and the microbiota-related functional predictions in 10 BE and 6 EAC patients compared with 10 controls, exploring also potential differences between the metaplastic mucosa (BEM) and the adjacent normal areas of BE patients (BEU). BEM and EAC showed a higher level of α and β-diversity. BEM evidenced a decrease of Streptococcus and an increase of Prevotella, Actinobacillus, Veillonella, and Leptotrichia. EAC displayed a striking reduction of Streptococcus, with an increase of Prevotella, Veillonella and Leptotrichia. LefSe analysis identified Leptotrichia as the main taxa distinguishing EAC. BEM showed a decreased α-diversity compared with BEU and a reduction of Bacteroidetes, Prevotella and Fusobacterium. Functional predictions identified peculiar profiles for each group with a high potential for replication and repair in BEM; an upregulated energy, replication and signaling metabolisms, with the fatty-acids biosynthesis and nitrogen and D-alanine pathways down-regulated in EAC. Our pilot study identifies a unique microbial structure and function profile for BE and EAC, as well as for metaplastic and near-normal areas. It proposes a new concept for BE, which could be intended not only as the histological, but, also, as the microbial closest precursor of EAC. This requires further larger follow-up studies, but opens intriguing horizons towards innovative diagnostic and therapeutic options for EAC.

Background and objectives: In recent years, many different culture-independent molecular techniques have been developed with the aim of investigating the not yet cultivated part of the resident flora of the oral cavity and of analyzing the peri-implant and periodontal flora both in healthy and diseased sites. The most used technologies are Roche 454 pyrosequencing, Illumina HiSeq/MiSeq, ABI SOLiD and Ion Torrent. Due to these methods, two different approaches are available: Metagenomics and the 16S gene analysis. A complementary strategy was also recently developed: Culturomics. Culturomics consists of different culture conditions that allow a very rapid bacterial identification. The focused question of this review was developed in PICO format in order to investigate the role of metagenomics, 16S gene analysis and culturomics (interventions) in the differential study (comparison) of the peri-implant and periodontal microbiome (outcome) in humans (participants). The secondary aim was the characterization of currents limits and future applications of the three techniques. Methods: The authors performed a literature search on three databases (Web of Science, Scopus and PubMed) from 01/01/2003 to 31/06/2019. Date of last search was: 25/08/19. Any type of article dealing with the analysis of periodontal and peri-implant flora with metagenomic, culturomic or 16S gene analysis was included. No language restrictions were applied. Risk of bias for RCT was assessed using the Cochrane collaboration’s tool whereas case-control and cohort studies were evaluated through the Newcastle–Ottawa scale. Results: The initial search resulted in 330 titles in total. After careful evaluation of all results no studies were found to satisfy the primary outcome of the present review. Hence a narrative review dealing with the secondary aim was performed. Conclusions: Metagenomic and 16S gene analysis approaches contributed in clarifying some crucial aspects of the oral microbiome. Based on the reported evidence some bacteria could be found around teeth and implants even in the absence of signs of inflammation and other species are more frequently found in supragingival peri-implant biofilm. Teeth and implants (even if adjacent) seem not to share the same microbiome and healthy teeth have a more diversified one. The same analyses also highlighted that the oral biofilm of smokers is composed by more periodontopathogen bacteria compared to non-smokers and that geographical location and ethnicity seem to play a role in bacterial composition. Culturomics, which has not yet been applied to the study of oral microbiota, consists of the use of different culture conditions and of the identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI–TOF MS) with the aim of increasing the bacterial repertoire and avoiding the limits of molecular methods. In order to better evaluate perspectives and limits of the all presented approaches further studies comparing the different molecular techniques are encouraged. This review received no funding.

The human gut microbiome (GM) is a complex ecosystem that includes numerous prokaryotic and eukaryotic inhabitants. The composition of GM can influence an array of host physiological functions including immune development. Accumulating evidence suggest that several members of non-bacterial microbiota, including protozoa and helminths, that were earlier considered as pathogens, could have a commensal or beneficial relationship with the host. Here we examine the most recent data from omics studies on prokaryota-meiofauna-host interaction as well as the impact of gut parasitome on gut bacterial ecology and its role as ‘immunological driver’ in health and disease to glimpse new therapeutic perspectives.

The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori , cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state ( H. pylori ). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities. Drug use or bacterial infection can cause significant alterations of gastric microbiome. Here, the authors show how advanced pattern recognition by nonlinear machine intelligence can help disclose a bacteria-metabolite network which enlightens mechanisms behind such perturbations.

The gut microbiota is composed of bacteria, archaea, phages, and protozoa. It is now well known that their mutual interactions and metabolism influence host organism pathophysiology. Over the years, there has been growing interest in the composition of the gut microbiota and intervention strategies in order to modulate it. Characterizing the gut microbial populations represents the first step to clarifying the impact on the health/illness equilibrium, and then developing potential tools suited for each clinical disorder. In this review, we discuss the current gut microbiota manipulation strategies available and their clinical applications in personalized medicine. Among them, FMT represents the most widely explored therapeutic tools as recent guidelines and standardization protocols, not only for intestinal disorders. On the other hand, the use of prebiotics and probiotics has evidence of encouraging findings on their safety, patient compliance, and inter-individual effectiveness. In recent years, avant-garde approaches have emerged, including engineered bacterial strains, phage therapy, and genome editing (CRISPR-Cas9), which require further investigation through clinical trials.

Background and objectives: Infections caused by resistant bacteria are a growing public health problem that is linked to many different causes, among them the antibiotics’ incorrect use plays an important role. According to the World Health Organization (WHO) the most dangerous behaviors are the early interruption of antibiotic therapy and the use of molecules without appropriate prescription. The authors conducted a systematic review to assess if antibiotic prescription with different regimens is connected to the onset of bacterial resistance. Methods: The authors performed an electronic and manual literature search on four databases (Web of Science, Scopus, PubMed, and Cochrane Register of Controlled Trials) from their inception to 15 June 2019. The date of the last search was 27 November 2019. Any article comparing cultural or genic analysis of resistance in patients that took antibiotics with at least two different regimens was included. No language restrictions were applied. Risk of bias for randomized controlled trials (RCTs) was assessed using the Cochrane collaboration’s tool whereas case-control and cohort studies were evaluated through the Newcastle–Ottawa scale. Results: The initial search resulted in a total of 1744 titles. After careful evaluation of all results, only three studies satisfied the outcome of the present review. From the qualitative analysis of data, it emerges that even if antibiotics are administered for a shorter period than the conventional one the species that inhabit the oral cavity can adapt quickly and express genes of antibiotic resistance. Additional evidence from this analysis is that not only does the proportion of resistant bacteria increase in the oral cavity, but also in more distant districts such as the intestine. Conclusions: Despite the great number of studies retrieved by electronic databases only few studies investigated the target of this review. The reason for this evidence is that it is not ethical to investigate and compare different antibiotic regimens, shorter or longer than the appropriate one. This evidence is applicable both to prophylactic administrations and to those aimed at treating infections. Besides this, the WHO affirms that, in the absence of infective complications, the prescription of antibiotic after every type of surgical intervention cannot be admitted and that studies dealing with antibiotic regimens that do not comply with drug’s pharmacodynamics characteristics cannot be ethically admitted. PROSPERO acknowledgement of receipt [149149].

[...]bacteria encode 100-fold more genes than the human genome. [...]the intestinal microbiota of CDI patients is characterized by a marked increase in Proteobacteria and a strong decrease in the Firmicutes/Bacteroidetes ratio. [...]the donor is first submitted to a medical questionnaire and then to serological and microbiological screening tests.