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Aldo Lorenzetti M.D, Internal Medicine & Hepatology, Milano - SIMEDET Delegate
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Persistent #microbiome alterations modulate the rate of post-dieting #weight regain

http://www.nature.com/nature/journal/vaap/ncurrent/full/nature20796.html


Together, our data highlight a possible microbiome contribution to accelerated post-dieting weight regain, and suggest that microbiome-targeting approaches may help to diagnose and treat this common disorder.
Oral #Microbiome Composition Reflects Prospective Risk for #Esophageal Cancers
http://cancerres.aacrjournals.org/content/77/23/6777

Bacteria may play a role in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although evidence is limited to cross-sectional studies. In this study, we examined the relationship of oral microbiota with EAC and ESCC risk in a prospective study nested in two cohorts. Oral bacteria were assessed using 16S rRNA gene sequencing in prediagnostic mouthwash samples from n = 81/160 EAC and n = 25/50 ESCC cases/matched controls. Findings were largely consistent across both cohorts. Metagenome content was predicted using PiCRUST. We examined associations between centered log-ratio transformed taxon or functional pathway abundances and risk using conditional logistic regression adjusting for BMI, smoking, and alcohol. We found the periodontal pathogen Tannerella forsythia to be associated with higher risk of EAC. Furthermore, we found that depletion of the commensal genus Neisseria and the species Streptococcus pneumoniae was associated with lower EAC risk. Bacterial biosynthesis of carotenoids was also associated with protection against EAC. Finally, the abundance of the periodontal pathogen Porphyromonas gingivalis trended with higher risk of ESCC. Overall, our findings have potential implications for the early detection and prevention of EAC and ESCC
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Gut #microbiome–mediated bile acid metabolism regulates #liver cancer via NKT cells

http://science.sciencemag.org/content/360/6391/eaan5931

Primary bile acids increased CXCL16 expression, whereas secondary bile acids showed the opposite effect. Removing gram-positive bacteria by antibiotic treatment with vancomycin, which contains the bacteria mediating primary-to-secondary bile acid conversion, was sufficient to induce hepatic NKT cell accumulation and decrease liver tumor growth. Feeding secondary bile acids or colonization of bile acid–metabolizing bacteria, reversed both NKT cell accumulation and inhibition of liver tumor growth in mice with altered gut commensal bacteria. In nontumor liver tissue from human patients with primary liver cancer, primary bile acid chenodeoxycholic acid (CDCA) levels correlated with CXCL16 expression, whereas an inverse correlation was observed with secondary bile acid glycolithocholate (GLCA), suggesting that the finding may apply to humans.

CONCLUSION
We describe a mechanism by which the gut microbiome uses bile acids as messengers to control a chemokine-dependent accumulation of hepatic NKT cells and antitumor immunity in the liver, against both primary and metastatic liver tumors. These findings not only have possible implications for future cancer therapeutic studies but also provide a link between the gut microbiome, its metabolites, and immune responses in the liver
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The gut #microbiome regulates the increases in #depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats

https://www.nature.com/articles/s41380-019-0380-x

Chronic exposure to stress is associated with increased incidence of depression, generalized anxiety, and PTSD. However, stress induces vulnerability to such disorders only in a sub-population of individuals, as others remain resilient. Inflammation has emerged as a putative mechanism for promoting stress vulnerability.

Because gut microbiota are important activators of inflammatory substances, we assessed the role of the gut microbiome in mediating vulnerability to repeated social defeat stress. We analyzed the fecal microbiome of control, SL/vulnerable, and LL/resilient rats using shotgun metagenome sequencing and observed increased expression of immune-modulating microbiota, such as Clostridia, in SL/vulnerable rats

..Taken together, the results suggest the gut microbiome contributes to the depression-like behavior and inflammatory processes in the vHPC of stress vulnerable individuals.
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Mapping human #microbiome #drug metabolism by gut bacteria and their genes

https://www.nature.com/articles/s41586-019-1291-3

Individuals vary widely in drug responses, which can be dangerous and expensive due to treatment delays and adverse effects. Growing evidence implicates the gut microbiome in this variability, however the molecular mechanisms remain largely unknown.

Here we measured the ability of 76 diverse human gut bacteria to metabolize 271 oral drugs and found that many of these drugs are chemically modified by microbes..

These causal links between microbiota gene content and metabolic activities connect interpersonal microbiome variability to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.
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Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans

Recent discoveries have implicated the gut #microbiome in the progression and severity of #Parkinson’s disease; however, how gut bacteria affect such neurodegenerative disorders remains unclear. Here, we report that the Bacillus subtilis probiotic strain PXN21 inhibits α-synuclein aggregation and clears preformed aggregates in an established Caenorhabditis elegans model of synucleinopathy. This protection is seen in young and aging animals and is partly mediated by DAF-16. Multiple B. subtilis strains trigger the protective effect via both spores and vegetative cells, partly due to a biofilm formation in the gut of the worms and the release of bacterial metabolites.

We identify several host metabolic pathways differentially regulated in response to probiotic exposure, including sphingolipid metabolism. We further demonstrate functional roles of the sphingolipid metabolism genes lagr-1, asm-3, and sptl-3 in the anti-aggregation effect. Our findings provide a basis for exploring the disease-modifying potential of B. subtilis as a dietary supplement.

https://bit.ly/2Gm0uMk
Sputum #microbiome profiles identify severe #asthma phenotypes of relative stability at 12-18 months
https://2medical.news/2020/05/03/sputum-microbiome-profiles-identify-severe-asthma-phenotypes-of-relative-stability-at-12-18-months/

..Data were available for 100 severe asthma subjects (median age: 55 yrs, 42% males). Two microbiome-driven clusters were identified, characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry, and concurrent asthma medications (all p-values <.05). Cluster 2 patients displayed a commensal-deficient bacterial profile which was associated with worse asthma outcomes compared to cluster 1. …
Adverse effects of electronic #cigarettes on the disease-naive oral #microbiome
https://2medical.news/2020/06/01/adverse-effects-of-electronic-cigarettes-on-the-disease-naive-oral-microbiome/

Six percent of Americans, including 3 million high schoolers, use e-cigarettes, which contain potentially toxic substances, volatile organic compounds, and metals. We present the first human study on the effects of e-cigarette exposure in the oral cavity. By interrogating both immunoinflammatory responses and microbial functional dynamics, we discovered pathogen overrepresentation, higher virulence signatures, and a brisk proinflammatory signal in clinically healthy e-cigarette users, equivalent to …