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1. Using Cultivated Microbial Communities To Dissect Microbiome Assembly: Challenges, Limitations, and the Path Ahead

   https://doi.org/10.1128/mSystems.00161-17  

   Wolfe, Benjamin E. (April 2018, mSystems)

   ABSTRACT As troves of microbiome sequencing data provide improved resolution of patterns of microbial diversity, new approaches are needed to understand what controls these patterns. Many microbial ecologists are using cultivated model microbial communities to address this challenge. These systems provide opportunities to identify drivers of microbiome assembly, but key challenges and limitations need to be carefully considered in their development, implementation, and interpretation. How well do model microbial communities mimic in vitro communities in terms of taxonomic diversity, trophic levels, intraspecific diversity, and the abiotic environment? What are the best ways to manipulate and measure inputs and outputs in model community experiments? In this perspective, I briefly address some of these challenges on the basis of our experience developing fermented food model communities. Future work integrating genetic and molecular approaches with cultivated model microbial communities will allow microbial ecology to develop a more mechanistic understanding of microbiome diversity. 

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2. The role of the microbiome in human disease

   Flowers, L. (February 2023, Biomedical journal of scientific technical research)

   Since the invention of the microscope, scientists have described microbial communities on living and non-living matter. In terms of human-associated microbes, scientists have documented the beneficial effects of the microbiota for many decades. Prophylactic effects include protection from pathogens, digestion potential, and the production of essential vitamins. However, recent high-throughput methodologies and analytical advances have accelerated microbiome science and our understanding of microbial diversity in living organisms. The microbiome denotes the complex network of all the microorganisms and microbial genes located in specific biotic or abiotic environments. We now realize the enormous diversity and functionality of the microbiota in humans and the endless benefits to health and disease. Dysbiosis facilitates the manufacture of various proinflammatory mediators, biochemical imbalances, and colonization of microbes associated with disease outcomes. Additional work is necessary to determine whether changes in the human microbiome are due to anthropogenic, genetic, or environmental variations. This review will present microbiome research studies focusing on human disease. The findings documented in this article offer optimism on the profound role microorganisms play in supporting human health and how pharmaceutical interactions targeting specific microbes can decrease the incidence of human disease caused by the ecological disturbance of the normal microbiota. 

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3. Environmental microbiome engineering for the mitigation of climate change

   https://doi.org/10.1111/gcb.16609  

   Silverstein, Michael R; Segrè, Daniel; Bhatnagar, Jennifer M (April 2023, Global Change Biology)

   Abstract Environmental microbiome engineering is emerging as a potential avenue for climate change mitigation. In this process, microbial inocula are introduced to natural microbial communities to tune activities that regulate the long‐term stabilization of carbon in ecosystems. In this review, we outline the process of environmental engineering and synthesize key considerations about ecosystem functions to target, means of sourcing microorganisms, strategies for designing microbial inocula, methods to deliver inocula, and the factors that enable inocula to establish within a resident community and modify an ecosystem function target. Recent work, enabled by high‐throughput technologies and modeling approaches, indicate that microbial inocula designed from the top‐down, particularly through directed evolution, may generally have a higher chance of establishing within existing microbial communities than other historical approaches to microbiome engineering. We address outstanding questions about the determinants of inocula establishment and provide suggestions for further research about the possibilities and challenges of environmental microbiome engineering as a tool to combat climate change. 

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4. Correlation between postmortem microbial signatures and substance abuse disorders

   https://doi.org/10.1371/journal.pone.0274401  

   Javan, Gulnaz T.; Wells, Tiara; Allen, Jamese; Visona, Silvia; Moretti, Matteo; Tipton, Craig; Scott, Latia; Finley, Sheree J. (September 2022, PLOS ONE)

   Staley, Christopher (Ed.)

   The microbiota gut-brain-axis is a bidirectional circuit that links the neural, endocrine, and immunological systems with gut microbial communities. The gut microbiome plays significant roles in human mind and behavior, specifically pain perception, learning capacity, memory, and temperament. Studies have shown that disruptions in the gut microbiota have been associated with substance use disorders. The interplay of gut microbiota in substance abuse disorders has not been elucidated; however, postmortem microbiome profiles may produce promising avenues for future forensic investigations. The goal of the current study was to determine gut microbiome composition in substance abuse disorder cases using transverse colon tissues of 21 drug overdose versus 19 non-overdose-related cases. We hypothesized that postmortem samples of the same cause of death will reveal similar microbial taxonomic relationships. We compared microbial diversity profiles using amplicon-based sequencing of the 16S rRNA gene V4 hypervariable region. The results demonstrated that the microbial abundance in younger-aged cases were found to have significantly more operational taxonomic units than older cases. Using weighted UniFrac analysis, the influence of substances in overdose cases was found to be a significant factor in determining microbiome similarity. The results also revealed that samples of the same cause of death cluster together, showing a high degree of similarity between samples and a low degree of similarity among samples of different causes of death. In conclusion, our examination of human transverse colon microflora in decomposing remains extends emerging literature on postmortem microbial communities, which will ultimately contribute to advanced knowledge of human putrefaction. 

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5. Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease

   https://doi.org/10.1128/mBio.00321-19  

   Aleti, Gajender; Baker, Jonathon L.; Tang, Xiaoyu; Alvarez, Ruth; Dinis, Márcia; Tran, Nini C.; Melnik, Alexey V.; Zhong, Cuncong; Ernst, Madeleine; Dorrestein, Pieter C.; et al (April 2019, mBio)

   ABSTRACT Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world’s most common chronic diseases. IMPORTANCE The healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world’s most common and costly chronic infectious diseases and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome and how it devolves in the case of two prominent diseases. 

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