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1. A Distinct Contractile Injection System Gene Cluster Found in a Majority of Healthy Adult Human Microbiomes

   https://doi.org/10.1128/mSystems.00648-20  

   Rojas, Maria I.; Cavalcanti, Giselle S.; McNair, Katelyn; Benler, Sean; Alker, Amanda T.; Cobián-Güemes, Ana G.; Giluso, Melissa; Levi, Kyle; Rohwer, Forest; Bailey, Barbara A.; et al (August 2020, mSystems)

   Gilbert, Jack A. (Ed.)

   ABSTRACT Many commensal bacteria antagonize each other or their host by producing syringe-like secretion systems called contractile injection systems (CIS). Members of the Bacteroidales family have been shown to produce only one type of CIS—a contact-dependent type 6 secretion system that mediates bacterium-bacterium interactions. Here, we show that a second distinct cluster of genes from Bacteroidales bacteria from the human microbiome may encode yet-uncharacterized injection systems that we term Bacteroidales injection systems (BIS). We found that BIS genes are present in the gut microbiomes of 99% of individuals from the United States and Europe and that BIS genes are more prevalent in the gut microbiomes of healthy individuals than in those individuals suffering from inflammatory bowel disease. Gene clusters similar to that of the BIS mediate interactions between bacteria and diverse eukaryotes, like amoeba, insects, and tubeworms. Our findings highlight the ubiquity of the BIS gene cluster in the human gut and emphasize the relevance of the gut microbiome to the human host. These results warrant investigations into the structure and function of the BIS and how they might mediate interactions between Bacteroidales bacteria and the human host or microbiome. IMPORTANCE To engage with host cells, diverse pathogenic bacteria produce syringe-like structures called contractile injection systems (CIS). CIS are evolutionarily related to the contractile tails of bacteriophages and are specialized to puncture membranes, often delivering effectors to target cells. Although CIS are key for pathogens to cause disease, paradoxically, similar injection systems have been identified within healthy human microbiome bacteria. Here, we show that gene clusters encoding a predicted CIS, which we term Bacteroidales injection systems (BIS), are present in the microbiomes of nearly all adult humans tested from Western countries. BIS genes are enriched within human gut microbiomes and are expressed both in vitro and in vivo . Further, a greater abundance of BIS genes is present within healthy gut microbiomes than in those humans with with inflammatory bowel disease (IBD). Our discovery provides a potentially distinct means by which our microbiome interacts with the human host or its microbiome. 

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2. Gut Microbiome: Profound Implications for Diet and Disease

   https://doi.org/10.3390/nu11071613  

   Hills, Ronald D.; Pontefract, Benjamin A.; Mishcon, Hillary R.; Black, Cody A.; Sutton, Steven C.; Theberge, Cory R. (July 2019, Nutrients)

   The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease. 

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3. Development of the intestinal microbiome in cystic fibrosis in early life

   https://doi.org/10.1128/msphere.00046-23  

   Price, Courtney E.; Hampton, Thomas H.; Valls, Rebecca A.; Barrack, Kaitlyn E.; O’Toole, George A.; Madan, Juliette C.; Coker, Modupe O. (August 2023, mSphere)

   Young, Vincent B. (Ed.)

   Cystic fibrosis is a heritable disease that disrupts ion transport at mucosal surfaces, causing a buildup of mucus and dysregulation of microbial communities in both the lungs and the intestines. Persons with CF are known to have dysbiotic gut microbial communities, but the development of these communities over time beginning at birth has not been thoroughly studied. Here, we describe an observation study following the development of the gut microbiome of cwCF throughout the first 4 years of life, during the critical window of both gut microbiome and immune development. Our findings indicate the possibility of the gut microbiota as a reservoir of airway pathogens and a surprisingly early indication of a microbiota associated with inflammatory bowel disease. 

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4. Optimal estimation of bacterial growth rates based on a permuted monotone matrix

   https://doi.org/10.1093/biomet/asaa082  

   Ma, Rong; Cai, T Tony; Li, Hongzhe (October 2020, Biometrika)

   Summary Motivated by the problem of estimating bacterial growth rates for genome assemblies from shotgun metagenomic data, we consider the permuted monotone matrix model $$Y=\Theta\Pi+Z$$ where $$Y\in \mathbb{R}^{n\times p}$$ is observed, $$\Theta\in \mathbb{R}^{n\times p}$$ is an unknown approximately rank-one signal matrix with monotone rows, $$\Pi \in \mathbb{R}^{p\times p}$$ is an unknown permutation matrix, and $$Z\in \mathbb{R}^{n\times p}$$ is the noise matrix. In this article we study estimation of the extreme values associated with the signal matrix $$\Theta$$, including its first and last columns and their difference. Treating these estimation problems as compound decision problems, minimax rate-optimal estimators are constructed using the spectral column-sorting method. Numerical experiments on simulated and synthetic microbiome metagenomic data are conducted, demonstrating the superiority of the proposed methods over existing alternatives. The methods are illustrated by comparing the growth rates of gut bacteria in inflammatory bowel disease patients and control subjects. 

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5. Next generation probiotics: Engineering live biotherapeutics

   https://doi.org/10.1016/j.biotechadv.2024.108336  

   Murali, Sanjeeva Kumar; Mansell, Thomas J (May 2024, Biotechnology Advances)

   The population dynamics of the human microbiome have been associated with inflammatory bowel disease, cancer, obesity, autoimmune diseases, and many other human disease states. An emerging paradigm in treatment is the administration of live engineered organisms, also called next-generation probiotics. However, the efficacy of these microbial therapies can be limited by the organism's overall performance in the harsh and nutrient-limited environment of the gut. In this review, we summarize the current state of the art use of bacterial and yeast strains as probiotics, highlight the recent development of genetic tools for engineering new therapeutic functions in these organisms, and report on the latest therapeutic applications of engineered probiotics, including recent clinical trials. We also discuss the supplementation of prebiotics as a method of manipulating the microbiome and improving the overall performance of engineered live biotherapeutics. 

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