Figure 1 - uploaded by Jeremy Paul Burton
Content may be subject to copyright.
Source publication
The conventional viewpoint of single-celled microbial metabolism fails to adequately depict energy flow at the systems level in host-adapted microbial communities. Emerging paradigms instead support that distinct microbiomes develop interconnected and interdependent electron transport chains that rely on cooperative production and sharing of bioene...
Contexts in source publication
Context 1
... their ubiquity and established properties may have caused them to be overlooked in the past, mounting evidence suggests that they can exert pleiotropic extracellular effects and that their co-production in microbial communities supports optimal adaptation ( Celis and Relman, 2020;Franco-Obregó n and Gilbert, 2017;Fritts et al., 2021). For example, they may function as critical mediators in the orchestration of a communally driven interspecies electron transport chain (ETC) that connects all members of a microbiota while synchronously supporting massive metabolic versatility at a fraction of the overhead cost relative to conventional (single-celled) metabolism (Figure 1). ...
Context 2
... swapping between cells can occur in many ways (e.g., hydrogen oxidation-reduction cycling, shuttle mediation, physical contact, and more [Stams et al., 2006]) but appears to be facilitated by much of the same (or highly similar) base bioenergetic machinery used in conventional (i.e., intracellular or single-celled) electron transport ( Fritts et al., 2021). This includes the many heme-containing molecules, quinone-based electron shuttles, and related B vitamin cofactors that are also abundantly shared within the pantryome (Figure 1). Exemplifying this, Light et al. (2018) recently elucidated in Listeria monocytogenes that B vitamin derivatives (e.g., riboflavin, flavin mononucleotide [FMN], flavin adenine dinucleotide [FAD]) could mediate EET transfer by acting as free molecule electron shuttles outside of the cell, thereby defying the conventional view that flavin-based compounds are prosthetic groups restricted to membrane bound or intracellular compartments ( Light et al., 2018). ...
Context 3
... increasing levels via administration of mixed SCFA enemas (acetate/propionate/butyrate) has been found to be more effective at producing clinical remission in ulcerative colitis (UC) patients than butyrate-only enemas ( Breuer et al., 1997;Hamer et al., 2010). Similar inverse disease associations are also seen between overall SCFA levels and risk of developing obesity, insulin resistance, and T2D (Belizá rio et al., 2018). On the contrary, evidence from mice studies suggests that high-dose propionate (oral supplementation) can impair insulin signaling (glucagon/FABP4) ( Tirosh et al., 2019), whereas overproduction of acetate by the gut microbiota (induced via excess dietary fructose) can lead to hepatic lipogenesis or ''fatty liver'' ( Zhao et al., 2020). ...
Context 4
... utilization of gases by methanogens, acetogens, or sulfate-reducing bacteria is critical, as accumulation otherwise inhibits the reoxidation of NADH, thereby collapsing acidogenicdriven SCFA cross-feeding networks ( Rey et al., 2010). Since high SCFA levels in the distal gut are thought to exert an overall positive metabolic effect on the host (Boulangé et al., 2016), maintaining or increasing SCFA generation represents an attractive target from a clinical perspective. Exploration of anaerobic processes in activated sludge bioreactors suggests that SCFA concentrations can be enhanced in one of three ways by either (1) increasing the total amount of biodegradable organic matter, (2) increasing acidogenic bacteria, or (3) decreasing methanogens ( Zuo et al., 2018). ...
Context 5
... exception is Gram-negative sulfate-reducing bacteria such as Desulfosarcina (previously Desulfobacteria) spp., which are (alongside Enterococcus spp.) important degraders of p-cresol (M€ uller et al., 2001;Vi- jayasarathy et al., 2020) and associated with a lower cardiometabolic disease risk ( Smith et al., 2019). The counterintuitive decrease of certain (beneficial) Firmicutes seen in atherosclerosis and T2D is thus likely resultant from p-cresol-induced depletion of commensal Bacteroides spp., major B vitamin producers that support host mitochondrial health as well as riboflavin shuttling-based extracellular electron transport in auxotrophic Firmicutes such as F. prausnitzii and R. intestinalis (Pankratova et al., 2018). ...
Similar publications
Purine auxotrophy is an abundant trait among eukaryotic parasites and a typical marker for many budding yeast strains. Supplementation with an additional purine source (such as adenine) is necessary to cultivate these strains. If not supplied in adequate amounts, purine starvation sets in. We explored purine starvation effects in a model organism,...
Ceriporiopsis subvermispora is a white-rot fungus with great potential for industrial and biotechnological applications, such as the pretreatment of lignocellulose in biorefineries, as it decomposes the lignin in the plant cell wall without causing severe cellulose degradation. A genetic transformation system was recently developed; however, gene-t...
Introduction
Thymine auxotrophic in vitro mutants of Escherichia coli were first reported in the mid-20th century. Later, thymine-dependent clinical strains of E . coli as well as other Enterobacterales, Enterococcus faecalis and Staphylococcus aureus have been recognized as the cause of persistent and recurrent infections.
Objectives
The aim of t...
Streptococcus suis , a common member of the porcine respiratory microbiota, can cause life-threatening diseases in pigs as well as humans. A previous study identified the gene trpX as conditionally essential for in vivo survival by intrathecal infection of pigs with a transposon library of S. suis strain 10. Here, we characterized trpX, encoding a...
Citations
... Interestingly, all vitamin synthesis pathways have been identified in human faecal samples through shotgun metagenomic sequencing, suggesting that the microbiota might have some roles in vitamin acquisition by the host, including vitamins that were previously not considered as microbially derived 46 . Not all bacteria can produce these vitamins de novo, but in an adapted microbial network, bacteria might exchange resources in the extracellular "pantryome" 47 to complete gaps in metabolic pathways. The "pantryome" concept is based on the idea that individual bacteria that lack some nutrients can take these nutrients from a pool of metabolites shared with other members of the microbiome and, in return, donate the excess metabolites back to the pool for other members to use. ...
... The contribution of the microbiota to vitamin absorption and activity has been overlooked in many current studies in which the role of the microbiota has been assessed in several diseases 47 . Gaps in the understanding of the role of vitamins and kidney stones have become particularly evident considering the uncertain history of vitamins and ...
... The idea of a role of gut microbiome in stone disease is supported by the strong association between oral antibiotic use and incidence of kidney stones 31 . The initial attempts kidney stone disease, and the evidence that gut bacteria are able to synthesize these vitamins 47,48 . ...
Calcium-based kidney stone disease is a highly prevalent and morbid condition, with an often complicated and multifactorial aetiology. An abundance of research on the role of specific vitamins (B6, C and D) in stone formation exists, but no consensus has been reached on how these vitamins influence stone disease. As a consequence of emerging research on the role of the gut microbiota in urolithiasis, previous notions on the contribution of these vitamins to urolithiasis are being reconsidered in the field, and investigation into previously overlooked vitamins (A, E and K) was expanded. Understanding how the microbiota influences host vitamin regulation could help to determine the role of vitamins in stone disease.
... Serum gut microbiome-derived metabolites, namely trimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAGln) have been established to be predictive of thrombotic cardiovascular diseases [8,9]. Gut commensals could also influence platelet function [10], VWF synthesis [11], and Vitamin K2 metabolism [12]. When the gut epithelial barrier is impaired by stress such as inflammation and viral infection, gut microbes, microbial products (e.g., lipopolysaccharides [LPS]), and metabolites (e.g., TMAO) translocate into the portal and then systemic circulation with resultant bacteremia and endotoxemia and potentially disseminated intravascular coagulation (DIC) [13]. ...
COVID-19 is characterized by a predominantly prothrombotic state, which underlies severe disease and poor outcomes. Imbalances of the gut microbiome have been linked with abnormal hemostatic processes. Understanding the relationship between the gut microbiome and abnormal coagulation parameters in COVID-19 could provide a novel framework for the diagnosis and management of COVID-related coagulopathies (CRC). This cross-sectional study used shotgun metagenomic sequencing to examine the gut microbiota of patients with CRC (n = 66) and compared it to COVID control (CCs) (n = 27) and non-COVID control (NCs) (n = 22) groups. Three, 1, and 3 taxa were found enriched in CRCs, CCs, and NCs. Next, random forest models using 7 microbial biomarkers and differential clinical characteristics were constructed and achieved strong diagnostic potential in distinguishing CRC. Specifically, the most promising biomarker species for CRC were Streptococcus thermophilus, Enterococcus faecium, and Citrobacter portucalensis. Conversely, Enterobacteriaceae family and Fusicatenibacter genus are potentially protective against CRC in COVID patients. We further identified 4 species contributing to 20 MetaCyc pathways that were differentially abundant among groups, with S. thermophilus as the main coding species in CRCs. Our findings suggest that the alterations of gut microbiota compositional and functional profiles may influence the pathogenesis of CRC and that microbiota-based diagnosis and treatment could potentially benefit COVID patients in preventing and alleviating thrombosis-related clinical outcomes.
... Multiple studies have highlighted the probiotic benefits of Lactiplantibacillus plantarum, such as, reducing host epithelial inflammation, altering host lipid metabolism, and exhibiting antihyperglycemic potential (34)(35)(36). Additionally, it is increasingly evident that microbes in the gut microbiome share and differentially utilize secreted factors like quinones and flavins to survive (37). We believe that the discovery of EET supported by flavins is of significant importance to understanding the dynamics of interspecies microbial energetics within the gut microbial community. ...
Lactic acid bacteria are named because of their nearly exclusive fermentative metabolism. Thus, the recent observation of EET activity—typically associated with anaerobic respiration—in this class of organisms has forced researchers to rethink the rules governing microbial metabolic strategies.
... SCFAs, the byproducts of dietary fiber in intestine during fermentation, are the most important energy substances of the epithelial lining of the colon [15]. SCFAs are known for their beneficial effects on intestinal barrier function, systemic anti-inflammatory effects, and their role in producing a fraction of the daily energy requirement of gut microbiota, and recently their role in urological disease has also been highlighted [16,17]. We briefly summarize studies reported so far on various axes related to the occurrence of urinary tract disease and the inflammasome and SCFAs supporting them. ...
Our knowledge that “urine is sterile” is no longer accepted after the development of a next-generation sequencing (NGS) test. Using NGS, microbiota in the human body were discovered, and it is expected that this will improve our understanding of human diseases. However, the mechanism involved in the effect of the microbiome on diseases is still poorly understood. Associations of gut microbiome with diseases have been recently reported. Based on such associations, bladder–gut–brain axis, gut–bladder axis, gut–vagina–bladder axis, and gut–kidney axis as novel mechanisms of action of the microbiome have been suggested. Each axis can influence the development and progression of disease through interactions. In these interactions, metabolites of the microbiome including short-chain fatty acids (SCFA) and the inflammasome play an important role. Inflammasomes are multiprotein oligomers that can initiate inflammatory responses. Inflammasomes can trigger inflammation and pyroptosis and ultimately contribute to disease development. SCFAs play an important role in immune cell migration, cytokine production, and maintenance of cellular homeostasis. Associations of inflammasomes with systemic diseases such as obesity and insulin resistance have been reported. The roles of inflammasomes and SCFAs in kidney, bladder, and prostate diseases have also been revealed recently.
... Over the last two decades, the microbiota has been largely studied in the context of human health and is linked with numerous pathological situations [8,11,17,[22][23][24]28,32,33,35,43,48,50,. Interestingly, the microbiota is also seen as a cornerstone to honeybee health, as for so many other living organisms. ...
... Pollen scarcity causes the atrophy of glands vital for breeding, and reduces body weight, lipid and protein body composition, and bee longevity. Honeybees need pollen sources as soon as the queen lays her eggs at the end of wintertime [23]. Moreover, a study shows that protein-and lipid-metabolic pathways promote detoxification within bees, such as pesticide detoxification, and this all year round [24][25][26]. ...
... Two other species clusters are related to Alphaproteobacteria: Alpha 1, which is similar to the Bartonella species, and Alpha 2 (Alpha 2-1, which is a gut specialist, and Alpha 2-2 Parasaccharibacter apium that commonly grows outside in the environment and is present in the larval gut, adult crop, nectar, honey, and hive materials, but is absent from the adult hindgut). Lactobacillus kunkei has been found in the hive, larval gut, adult crop, honey, and nectar, but not in the adult hindgut [11,23,24,60,62,63,67,[69][70][71][72]76,77,79,82,83,87,[129][130][131]. Some other clusters of Bacteroidetes may be present in low abundance, or Enterobacteriaceae may be present with common insect pathogens [59,60]. ...
Climate change, loss of plant biodiversity, burdens caused by new pathogens, predators, and toxins due to human disturbance and activity are significant causes of the loss of bee colonies and wild bees. The aim of this review is to highlight some possible strategies that could help develop bee resilience in facing their changing environments. Scientists underline the importance of the links between nutrition, microbiota, and immune and neuroendocrine stress resistance of bees. Nutrition with special care for plant-derived molecules may play a major role in bee colony health. Studies have highlighted the importance of pollen, essential oils, plant resins, and leaves or fungi as sources of fundamental nutrients for the development and longevity of a honeybee colony. The microbiota is also considered as a key factor in bee physiology and a cornerstone between nutrition, metabolism, growth, health, and pathogen resistance. Another stressor is the varroa mite parasite. This parasite is a major concern for beekeepers and needs specific strategies to reduce its severe impact on honeybees. Here we discuss how helping bees to thrive, especially through changing environments, is of great concern for beekeepers and scientists.
... [6][7][8] These may take the form of specific co-abundance or interaction modules (IMs), [6][7][8] or reflect broader aspects of microbial community assembly observed across human populations (such as community types or enterotypes) 9,10 which likely represent differential nutritional and bioenergetic signatures. 11 can be readily related to genome evolution, 14 the higher-order processes constraining emergent structures are yet to be defined, partially due to the inherent complexity within the community. ...
... Mechanistic drivers of higher order units in the gut microbiome, which are responsible for the biological processes that impact health, can be identified by characterizing the metabolic attributes and nutritional requirements of gut strains. Vitamins participate in crucial intracellular metabolism but also constitute part of the extracellular machinery that contributes to community bioenergetic balance, 11 positioning them as potential mechanistic drivers of gut higher order units. Relying on GEMNAST, we have performed a metabolic exploration of the vitamin nutritional dimension of gut strain metabolism as represented in AGORA GSMs to determine the role of this aspect of strain metabolism in community structure. ...
Human gut microbiome structure and emergent metabolic outputs impact health outcomes. However, what drives such community characteristics remains underexplored. Here, we rely on high throughput genomic reconstruction modeling, to infer the metabolic attributes and nutritional requirements of 816 gut strains, via a framework termed GEMNAST. This has been performed in terms of a group of human vitamins to examine the role vitamin exchanges have at different levels of community organization. We find that only 91 strains can satisfy their vitamin requirements (prototrophs) while the rest show various degrees of auxotrophy/specialization, highlighting their dependence on external sources, such as other members of the microbial community. Further, 79% of the strains in our sample were mapped to 11 distinct vitamin requirement profiles with low phylogenetic consistency. Yet, we find that human gut microbial community enterotype indicators display marked metabolic differences. Prevotella strains display a metabolic profile that can be complemented by strains from other genera often associated with the Prevotella enterotype and agrarian diets, while Bacteroides strains occupy a prototrophic profile. Finally, we identify pre-defined interaction modules (IMs) of gut species from human and mice predicted to be driven by, or highly independent of vitamin exchanges. Our analysis provides mechanistic grounding to gut microbiome stability and to co-abundance-based observations, a fundamental step toward understanding emergent processes that influence health outcomes. Further, our work opens a path to future explorations in the field through applications of GEMNAST to additional nutritional dimensions.
... Mounting evidence has linked the gut microbiota to health status in humans. It has become evident that gut microbes play a fundamental role in human nutrition and metabolism (1,2) and that alterations in microbiota composition, diversity and function may have direct implications for metabolic derangements including type 2 diabetes and associated pre-conditions (1,3). This insight has led to extensive research to identify microbial taxa and functions which could dictate or be targets for preventative actions and treatment, including dietary strategies (4)(5)(6). ...
... Mounting evidence has linked the gut microbiota to health status in humans. It has become evident that gut microbes play a fundamental role in human nutrition and metabolism (1,2) and that alterations in microbiota composition, diversity and function may have direct implications for metabolic derangements including type 2 diabetes and associated pre-conditions (1,3). This insight has led to extensive research to identify microbial taxa and functions which could dictate or be targets for preventative actions and treatment, including dietary strategies (4)(5)(6). ...
The gut microbiota plays a fundamental role in human nutrition and metabolism and may have direct implications for type 2 diabetes and associated pre-conditions. An improved understanding of relationships between human gut microbiota and glucose metabolism could lead to novel opportunities for type 2 diabetes prevention, but human observational studies reporting on such findings have not been extensively reviewed. Here, we review the literature on associations between gut microbiota and markers and stages of glucose dysregulation and insulin resistance in healthy adults and in adults with metabolic disease and risk factors. We present the current evidence for identified key bacteria and their potential roles in glucose metabolism independently of overweight, obesity and metabolic drugs. We provide support for short-chain fatty acids (SCFA) mediating such effects and discuss the role of diet and gut microbiota x diet derived metabolites. From 5983 initially identified PubMed records, 45 original studies were eligible and reviewed. Alpha diversity and 45 bacterial taxa were associated with selected outcomes. Six taxa were most frequently associated with glucose metabolism: Akkermansia muciniphila, Bifidobacterium longum, Clostridium leptum group, Faecalibacterium prausnitzii and Faecalibacterium (inversely associated) and Dorea (directly associated). For Dorea and A. muciniphila, associations were independent of metabolic drugs and body measures. For A. muciniphila and F. prausnitzii, limited evidence supported SCFA-mediation of potential effects on glucose metabolism. We conclude that observational studies applying metagenomics sequencing to identify species-level relationships are warranted, as are studies accounting for confounding factors and investigating SCFA and postprandial glucose metabolism. Such advances in the field will, together with mechanistic and prospective studies and investigations into diet-gut microbiota interactions, have the potential to bring critical insight into roles of gut microbiota and microbial metabolites in human glucose metabolism and to contribute towards the development of novel prevention strategies for type 2 diabetes, including precision nutrition.
... Critical key metabolism research areas include contractile function, insulin sensitivity, mitochondrial function, energy efficiency and exercise therapy. Lastly, a rapidly expanding area of metabolism research is the gut microbiome in maintaining metabolic homeostasis and immune balance (Daisley et al., 2021). Although the ability for the gut microbiome to maintain immune balance has been extensively investigated, major gaps exist in our knowledge of the mechanism by which the gut microbiome contributes to physiologic homeostasis and metabolism. ...
... Multiple studies have highlighted the probiotic benefits of Lactiplantibacillus plantarum, such as, reducing host epithelial inflammation, altering host lipid metabolism, and exhibiting antihyperglycemic potential (34)(35)(36). Additionally, it is increasingly evident that microbes in the gut microbiome share and differentially utilize secreted factors like quinones and flavins to survive (37). We believe that the discovery of EET supported by flavins is of significant importance to understanding the dynamics of interspecies microbial energetics within the gut microbial community. ...
Lactiplantibacillus plantarum is a lactic acid bacteria that is commonly found in the human gut and fermented food products. Despite its overwhelmingly fermentative metabolism, this microbe can perform extracellular electron transfer (EET) when provided with an exogenous quinone, 1,4-dihydroxy-2-naphthoic acid (DHNA) and riboflavin. However, the separate roles of DHNA and riboflavin in EET in L. plantarum has remained unclear. Here we seek to understand the role of quinones and flavins for EET by monitoring iron and anode reduction in the presence and absence of these small molecules. We found that either addition of DHNA or riboflavin can support robust iron reduction, indicating electron transfer to extracellular iron occurs through both flavin-dependent and DHNA-dependent routes. Using genetic mutants of L. plantarum , we found that flavin-dependent iron reduction requires Ndh2 and EetA, while DHNA-dependent iron reduction largely relies on Ndh2 and PplA. In contrast to iron reduction, DHNA-containing media supported more robust anode reduction than riboflavin-containing media, suggesting electron transfer to an anode proceeds most efficiently through the DHNA-dependent pathway. Furthermore, we found that flavin-dependent anode reduction requires EetA, Ndh2, and PplA, while DHNA-dependent anode reduction requires Ndh2 and PplA. Taken together, we identify multiple EET routes utilized by L. plantarum and show that the EET route depends on access to environmental biomolecules and on the extracellular electron acceptor. This work expands our molecular-level understanding of EET in Gram-positive microbes and provides additional opportunities to manipulate EET for biotechnology.
Importance
Lactic acid bacteria are named because of their nearly exclusive fermentative metabolism. Thus, the recent observation of EET activity - typically associated with anaerobic respiration - in this class of organisms has forced researchers to rethink the rules governing microbial metabolic strategies. Our identification of multiple routes for EET in L. plantarum that depend on two separate redox active small molecules expands our understanding of how microbes metabolically adapt to different environments to gain an energetic edge and how these processes can be manipulated for biotechnological uses. Understanding the role of EET in lactic acid bacteria is of great importance due to the significance of lactic acid bacteria in agriculture, bioremediation, food production, and gut health. Furthermore, the maintenance of multiple EET routes speak to the importance of this process to function in a variety of environmental conditions.
... In comparison to infection-causing pathogens, evolutionarily well-adapted symbionts often demonstrate genetic minimalism and auxotrophy, necessitating extracellular cooperative sharing of micronutrients [41,47,48]. Recent evidence suggests that welladapted microbiomes develop an interconnected electron transport chain, with key resources including aromatic amino acids, metabolic cofactors (B vitamins), menaquinones (vitamin K2), hemes, and short-chain fatty acids being shared in the extracellular space [41]. ...
... In comparison to infection-causing pathogens, evolutionarily well-adapted symbionts often demonstrate genetic minimalism and auxotrophy, necessitating extracellular cooperative sharing of micronutrients [41,47,48]. Recent evidence suggests that welladapted microbiomes develop an interconnected electron transport chain, with key resources including aromatic amino acids, metabolic cofactors (B vitamins), menaquinones (vitamin K2), hemes, and short-chain fatty acids being shared in the extracellular space [41]. This benefits not only the other microbes in the resource-sharing network, but also the host, because the microbiota produces these constituents at biologically meaningful concentrations for host utilization [41,49]. ...
... Recent evidence suggests that welladapted microbiomes develop an interconnected electron transport chain, with key resources including aromatic amino acids, metabolic cofactors (B vitamins), menaquinones (vitamin K2), hemes, and short-chain fatty acids being shared in the extracellular space [41]. This benefits not only the other microbes in the resource-sharing network, but also the host, because the microbiota produces these constituents at biologically meaningful concentrations for host utilization [41,49]. Importantly, some of the micronutrients known to be produced or modified by the gut microbiota may be deficient in astronauts during spaceflight [50,51]. ...
The microbiota is important for immune modulation, nutrient acquisition, vitamin production, and other aspects for long-term human health. Isolated model organisms can lose microbial diversity over time and humans are likely the same. Decreasing microbial diversity and the subsequent loss of function may accelerate disease progression on Earth, and to an even greater degree in space. For this reason, maintaining a healthy microbiome during spaceflight has recently garnered consideration. Diet, lifestyle, and consumption of beneficial microbes can shape the microbiota, but the replenishment we attain from environmental exposure to microbes is important too. Probiotics, prebiotics, fermented foods, fecal microbiota transplantation (FMT), and other methods of microbiota modulation currently available may be of benefit for shorter trips, but may not be viable options to overcome the unique challenges faced in long-term space travel. Novel fermented food products with particular impact on gut health, immune modulation, and other space-targeted health outcomes are worthy of exploration. Further consideration of potential microbial replenishment to humans, including from environmental sources to maintain a healthy microbiome, may also be required.
