The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease Multiple factors contribute to the establishment of the human gut microbiota during infancy Diet is considered as one of the main drivers in shaping the gut microbiota across the life time Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions

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Introduction to the human gut microbiota

https://www.journal-of-hepatology.eu/article/S0168-8278(13)00887-8/pdf

Altered profile of human gut microbiome is associated with cirrhosis and its complications

Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT.

The widespread use of antibiotics in the past 80 years has saved millions of human lives, facilitated technological progress and killed incalculable numbers of microbes, both pathogenic and commensal. Human-associated microbes perform an array of important functions, and we are now just beginning to understand the ways in which antibiotics have reshaped their ecology and the functional consequences of these changes. Mounting evidence shows that antibiotics influence the function of the immune system, our ability to resist infection, and our capacity for processing food. Therefore, it is now more important than ever to revisit how we use antibiotics. This review summarizes current research on the short-term and long-term consequences of antibiotic use on the human microbiome, from early life to adulthood, and its effect on diseases such as malnutrition, obesity, diabetes, and Clostridium difficile infection. Motivated by the consequences of inappropriate antibiotic use, we explore recent progress in the development of antivirulence approaches for resisting infection while minimizing resistance to therapy. We close the article by discussing probiotics and fecal microbiota transplants, which promise to restore the microbiota after damage of the microbiome. Together, the results of studies in this field emphasize the importance of developing a mechanistic understanding of gut ecology to enable the development of new therapeutic strategies and to rationally limit the use of antibiotic compounds.

/pdf/the-effects-of-antibiotics-on-the-microbiome-throughout-1ozpxpo73d.pdf

The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation

The human microbiome is overly exposed to antibiotics, due, not only to their medical use, but also to their utilization in farm animals and crops. Microbiome composition can be rapidly altered by exposure to antibiotics, with potential immediate effects on health, for instance through the selection of resistant opportunistic pathogens that can cause acute disease. Microbiome alterations induced by antibiotics can also indirectly affect health in the long-term. The mutualistic microbes in the human body interact with many physiological processes, and participate in the regulation of immune and metabolic homeostasis. Therefore, antibiotic exposure can alter many basic physiological equilibria, promoting long-term disease. In addition, excessive antibiotic use fosters bacterial resistance, and the overly exposed human microbiome has become a significant reservoir of resistance genes, contributing to the increasing difficulty in controlling bacterial infections. Here, the complex relationships between antibiotics and the human microbiome are reviewed, with focus on the intestinal microbiota, addressing (1) the effects of antibiotic use on the composition and function of the gut microbiota, (2) the impact of antibiotic-induced microbiota alterations on immunity, metabolism, and health, and (3) the role of the gut microbiota as a reservoir of antibiotic resistances.

/pdf/antibiotics-and-the-human-gut-microbiome-dysbioses-and-1ph182qns5.pdf

Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances

It is known that the gastrointestinal tract (GIT) microbiota responds to different antibiotics in different ways and that while some antibiotics do not induce disturbances of the community, others drastically influence the richness, diversity, and prevalence of bacterial taxa. However, the metabolic consequences thereof, independent of the degree of the community shifts, are not clearly understood. In a recent article, we used an integrative OMICS approach to provide new insights into the metabolic shifts caused by antibiotic disturbance. The study presented here further suggests that specific bacterial lineage blooms occurring at defined stages of antibiotic intervention are mostly associated with organisms that possess improved survival and colonization mechanisms, such as those of the Enterococcus, Blautia, Faecalibacterium, and Akkermansia genera. The study also provides an overview of the most variable metabolic functions affected as a consequence of a β-lactam antibiotic intervention. Thus, we observed that anabolic sugar metabolism, the production of acetyl donors and the synthesis and degradation of intestinal/colonic epithelium components were among the most variable functions during the intervention. We are aware that these results have been established with a single patient and will require further confirmation with a larger group of individuals and with other antibiotics. Future directions for exploration of the effects of antibiotic interventions are discussed.

https://gut.bmj.com/content/gutjnl/62/11/1591.full.pdf

Gut microbiota disturbance during antibiotic therapy: a multi-omic approach.

For eight acrylates, three methacrylates, and three propiolates as three subclasses of α,β-unsaturated esters, short-term and long-term bacterial toxicity with Vibrio fischeri was determined in terms of EC(50) (effective concentration 50%) values for the 30-min bioluminescence and 24-h growth inhibition. To this end, experimental exposure concentrations were corrected for volatilization through a thermodynamic model based on Henry's law constant of the compounds. Moreover, toxicity enhancements T(e) as the ratio of narcosis-predicted over actual EC(50) were determined and discussed in terms of underlying mechanisms of reaction of the electrophiles with endogenous nucleophiles such as glutathione (GSH) and proteins. Overall, log EC(50) [M] ranges from -2.28 to -3.70 (30 min) and from -2.80 to -5.28 (24 h), respectively, indicating a significantly larger sensitivity of the growth inhibition bioassay for the reactive toxicity of these Michael acceptors. The latter is also reflected in the observed toxicity enhancements, where log T(e) > 1 was obtained for only 5 of 14 30-min EC(50) values but for 11 of 13 24-h EC(50) values. Moreover, the average long-term to short-term difference in log T(e) is 1 unit for the acrylates and 0.7 units for both methacrylates and propiolates. Methacrylates exert narcosis-level toxicity except for the methyl derivative in the long-term assay. The log EC(50) (24 h) of a subset of 10 mostly excess-toxic acrylates and a propiolate correlates with their logarithmic rate constants of reaction with GSH, log k(GSH), significantly more than with log K(ow) (r(2) 0.76 vs 0.47), yielding a respective regression rms of 0.34 log units. For allyl and propargyl acrylate as well as propargyl methacrylate, the observed excess toxicity is likely caused by initial enzymatic hydrolysis and subsequent oxidation of the α,β-unsaturated alcohols to the respective carbonyls. The latter shows that in the context of nonanimal testing schemes such as for REACH, the metabolic capacity of in vitro screens requires attention.

Kathleen Eismann

Papers

Gut microbiota disturbance during antibiotic therapy: a multi-omic approach.

Structural alerts for the excess toxicity of acrylates, methacrylates, and propiolates derived from their short-term and long-term bacterial toxicity.