scholarly journals The Predicted Metabolic Function of the Gut Microbiota of Drosophila melanogaster

2021 ◽  
Author(s):  
Nana Y.D. Ankrah ◽  
Brandon E. Barker ◽  
Joan Song ◽  
Cindy Wu ◽  
John G. McMullen ◽  
...  

ABSTRACTAn important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and its impact on host physiology. This research can be confounded by poorly-understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multi-way interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the Drosophila gut microbiome (from single taxa to the five-member community of Acetobacter and Lactobacillus species) under three nutrient regimes. We show that the metabolic function of Drosophila gut bacteria is dynamic, influenced by community composition and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle including 2-oxoglutarate and succinate are produced at high flux and cross-fed between bacterial taxa suggesting important roles for TCA cycle intermediates in modulating Drosophila gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host.IMPORTANCEDrosophila is an important model for microbiome research partly because of the low complexity of its mostly culturable gut microbiota. Our current understanding of how Drosophila interacts with its gut microbes and how these interactions influence host traits derives almost entirely from empirical studies that focus on individual microbial taxa or classes of metabolites. These studies have failed to capture fully the complexity of metabolic interactions that occur between host and microbe. To overcome this limitation, we reconstructed and analyzed 31 metabolic models for every combination of the five principal bacterial taxa in the gut microbiome of Drosophila. This revealed that metabolic interactions between between Drosophila gut bacterial taxa are highly dynamic and influenced by co-occurring bacteria and nutrient availability. Our results generate testable hypothesis about among-microbe ecological interactions in the Drosophila gut and the diversity of metabolites available to influence host traits.

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Nana Y. D. Ankrah ◽  
Brandon E. Barker ◽  
Joan Song ◽  
Cindy Wu ◽  
John G. McMullen ◽  
...  

ABSTRACT An important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and their impact on host physiology. This research can be confounded by poorly understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multiway interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the Drosophila gut microbiome (from single taxa to the five-member community of Acetobacter and Lactobacillus species) under three nutrient regimes. We show that the metabolic function of Drosophila gut bacteria is dynamic, influenced by community composition, and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that, in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle, including 2-oxoglutarate and succinate, are produced at high flux and cross-fed between bacterial taxa, suggesting important roles for TCA cycle intermediates in modulating Drosophila gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host. IMPORTANCE Drosophila is an important model for microbiome research partly because of the low complexity of its mostly culturable gut microbiota. Our current understanding of how Drosophila interacts with its gut microbes and how these interactions influence host traits derives almost entirely from empirical studies that focus on individual microbial taxa or classes of metabolites. These studies have failed to capture fully the complexity of metabolic interactions that occur between host and microbe. To overcome this limitation, we reconstructed and analyzed 31 metabolic models for every combination of the five principal bacterial taxa in the gut microbiome of Drosophila. This revealed that metabolic interactions between Drosophila gut bacterial taxa are highly dynamic and influenced by cooccurring bacteria and nutrient availability. Our results generate testable hypotheses about among-microbe ecological interactions in the Drosophila gut and the diversity of metabolites available to influence host traits.


Author(s):  
Sidharth P Mishra ◽  
Shalini Jain ◽  
Subhash Taraphder ◽  
Hariom Yadav

Abstract Decade-old studies have demonstrated that microbes living in our gut (microbiota) contribute to both maintaining normal metabolic function and to the pathology of metabolic diseases, such as obesity and diabetes. Emerging evidence suggests that gut microbiota influences the personalized effects of diets and drugs and impact the gut–brain axis and leaky gut inflammation to control metabolic function/diseases. Gut microbiota can be an ideal source of prognostic markers and therapies for metabolic diseases. Here we discuss the emerging concepts in the area of microbiota and metabolic interactions in personalized nutrition, drug response, and disease prognosis.


2020 ◽  
Author(s):  
Daniela Gaio ◽  
Matthew Z DeMaere ◽  
Kay Anantanawat ◽  
Graeme J Eamens ◽  
Michael Liu ◽  
...  

Abstract BackgroundEarly weaning and intensive farming practices predispose piglets to the development of infectious and often lethal diseases, against which antibiotics are used. Besides contributing to the build-up of antimicrobial resistance, antibiotics are known to modulate the gut microbial composition. Studies have previously investigated the effects of probiotics as alternatives to antibiotic treatment for the prevention of post-weaning diarrhea. In order to describe the post-weaning gut microbiota, and the effects of two probiotics formulations and of intramuscular antibiotic treatment on the gut microbiota, we processed over 800 faecal time-series samples from 126 piglets and 42 sows, generating over 8Tbp of metagenomic shotgun sequence data. Here we describe the animal trial procedures, the generation of our metagenomic dataset and the analysis of the microbial community composition using a phylogenetic framework.ResultsFactors such as age, litter effects, and breed, by significantly correlating with gut microbial community shifts, can be major confounding factors in the assessment of treatment effects. Intramuscular antibiotic treatment and probiotic treatments were found to correlate with alpha and beta diversity, as well as with a transient establishment of Mollicutes and Lactobacillales, respectively. We found the abundance of certain taxa to correlate with weight gain.ConclusionsOur findings demonstrate that breed, litter, and age, are important contributors to variation in the community composition, and that treatment effects of the antibiotic and probiotic treatments were subtle, while host age was the dominant factor in shaping the gut microbiota of piglets after weaning. The current study shows, by means of a phylogenetic diversity framework, that the post-weaning pig gut microbiome appears to follow a highly structured developmental program with characteristic post-weaning changes that can distinguish hosts that were born as little as two days apart in the second month of life.


2021 ◽  
Vol 9 (12) ◽  
pp. 2583
Author(s):  
Leon M. T. Dicks ◽  
Diron Hurn ◽  
Demi Hermanus

Bacteria in the gut microbiome plays an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. Apart from physiological and structural changes brought about by gut bacteria on entero-epithelial cells and mucus layers, a vast number of signals generated in the gastro-intestinal tract (GIT) reaches the brain via the vagus nerve. Research on the gut–brain axis (GBA) has mostly been devoted to digestive functions and satiety. Less papers have been published on the role gut microbiota play in mood, cognitive behavior and neuropsychiatric disorders such as autism, depression and schizophrenia. Whether we will be able to fully decipher the connection between gut microbiota and mental health is debatable, especially since the gut microbiome is diverse, everchanging and highly responsive to external stimuli. Nevertheless, the more we discover about the gut microbiome and the more we learn about the GBA, the greater the chance of developing novel therapeutics, probiotics and psychobiotics to treat gastro-intestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), but also improve cognitive functions and prevent or treat mental disorders. In this review we focus on the influence gut bacteria and their metabolites have on neuropsychiatric disorders.


2020 ◽  
Author(s):  
Jiankai Wei ◽  
Hongwei Gao ◽  
Yang Yang ◽  
Haiming Liu ◽  
Haiyan Yu ◽  
...  

Abstract Background Gut microbiota plays important roles in host animal metabolism, homeostasis and environmental adaptation. However, the interplay between the gut microbiome and urochordate ascidian, the most closet relative of vertebrate, remains less explored. In this study, we characterized the gut microbial communities of urochordate ascidian ( Halocynthia roretzi ) across the changes of season and starvation stress using a comprehensive set of omic approaches including 16S rRNA gene amplicon sequencing, shotgun metagenomics, metabolomic profiling, and transcriptome sequencing. Results The 16S rRNA gene amplicon profiling revealed that ascidians harbor indigenous gut microbiota distinctly different to the marine microbial community and significant variations in composition and abundance of gut bacteria, with predominant bacterial orders representing each season. Depressed alpha-diversities of gut microbiota were observed across starvation stress when compared to the communities in aquafarm condition. Synechococcales involving photosynthesis and its related biosynthesis was reduced in abundance while the enrichments of Xanthomonadales and Legionellales may facilitate bile acid biosynthesis during starvation. Metabolomics analysis found that long chain fatty acids, linolenic acid,cyanoamino acid, and pigments derived from gut bacteria were upregulated, suggesting a beneficial contribution of the gut microbiome to the ascidian under starvation stress. Conclusions Our findings revealed seasonal variation of ascidian gut microbiota. Defense and energy-associated metabolites derived from gut microbiome may provide an adaptive interplay between gut microbiome and ascidian host that maintains a beneficial metabolic system across season and starvation stress. The diversity-generating metabolisms from both microbiota and host might lead to the co-evolution and environmental adaptation.


2020 ◽  
Author(s):  
Jiankai Wei ◽  
Hongwei Gao ◽  
Yang Yang ◽  
Haiming Liu ◽  
Haiyan Yu ◽  
...  

Abstract BackgroundGut microbiota plays important roles in host animal physiology, homeostasis, metabolism, and environmental adaptation while the interplay between the gut microbiome and urochordate ascidian, the most closet relative of vertebrate, remains less explored. In this study, we characterized the gut microbial communities of urochordate ascidian (Halocynthia roretzi) across the changes of season and starvation stress using a comprehensive set of omic approaches including 16S rRNA, metagenomic, metabiotic, and transcriptome sequencing.ResultsThe 16S rRNA amplicon profiling revealed that ascidians harbor indigenous gut microbiota distinctly different to the marine microbial community and significant variations in composition and abundance of gut bacteria, with predominant bacterial orders representing each season. Depressed alpha-diversities of gut microbiota were observed across starvation stress when compared with the communities in aquafarm condition. Synechococcales involving photosynthesis and its related biosynthesis was reduced in abundance while the enrichments of Xanthomonadales and Legionellales may facilitate bile acid biosynthesis in starvation stress condition. Meanwhile, the metabolomics analysis found that the long chain fatty acids, linolenic acid, cyanoamino acid, and pigments derived from gut bacteria were upregulated, suggesting a beneficial contribution of the gut microbiome to ascidian under starvation stress.ConclusionsOur results revealed the seasonal variation of ascidian gut microbiota. Furthermore, we found that the defense and energy-associated metabolites derived from gut microbiome were responded to the starvation stress. The data provide insights into understanding the adaptive interplay between the gut microbiome and ascidian host that maintains a beneficial metabolic system across season and starvation stress. The diversity-generating metabolisms from both microbiota and host might lead to the co-evolution and environmental adaptation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra A. Appiah ◽  
Christine L. Foxx ◽  
Dominik Langgartner ◽  
Annette Palmer ◽  
Cristian A. Zambrano ◽  
...  

AbstractSevere injuries are frequently accompanied by hemorrhagic shock and harbor an increased risk for complications. Local or systemic inflammation after trauma/hemorrhage may lead to a leaky intestinal epithelial barrier and subsequent translocation of gut microbiota, potentially worsening outcomes. To evaluate the extent with which trauma affects the gut microbiota composition, we performed a post hoc analysis of a murine model of polytrauma and hemorrhage. Four hours after injury, organs and plasma samples were collected, and the diversity and composition of the cecal microbiome were evaluated using 16S rRNA gene sequencing. Although cecal microbial alpha diversity and microbial community composition were not found to be different between experimental groups, norepinephrine support in shock animals resulted in increased alpha diversity, as indicated by higher numbers of distinct microbial features. We observed that the concentrations of proinflammatory mediators in plasma and intestinal tissue were associated with measures of microbial alpha and beta diversity and the presence of specific microbial drivers of inflammation, suggesting that the composition of the gut microbiome at the time of trauma, or shortly after trauma exposure, may play an important role in determining physiological outcomes. In conclusion, we found associations between measures of gut microbial alpha and beta diversity and the severity of systemic and local gut inflammation. Furthermore, our data suggest that four hours following injury is too early for development of global changes in the alpha diversity or community composition of the intestinal microbiome. Future investigations with increased temporal-spatial resolution are needed in order to fully elucidate the effects of trauma and shock on the gut microbiome, biological signatures of inflammation, and proximal and distal outcomes.


2021 ◽  
Author(s):  
Kumaresan Nallasamy ◽  
Sucheta Gokhale ◽  
Anirban Bhaduri ◽  
Ashok Kumar Dubey

Abstract In the current study, we aimed to investigate the association between gut microbiome composition and two physiological factors, BMI and age. We did not observe a significant relationship between occurrence of gut bacteria with BMI or age alone. On the other hand, we observed BMI and age together played an important role in impacting gut microbiota composition. Comparison of the microbiota of normal and obese subjects for the each of 20s and 50s group revealed 13 gut bacteria that show significantly different relative abundance in the two groups. We observed that certain organisms show opposite trends within the two age groups. Haemophilus parainfluenzae relative abundance was found to be increased in obese-20s group while reduced in obese-50s group. Relative abundance of organisms such as Mitsuokella jalaludini and Blautia obeum were reduced in obese-20s group while increased in obese-50s group as compared to the normal subjects of respective age group. On the other hand, a reduction in the average relative abundance of both M. jalaludini and B. obeum for obese group as compared to the normal in pan-India only BMI-based group comparison. While studying obesity-related gut microbiota changes, it is critical to consider multiple factors such as age and geography into the study design.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Cuesta-Maté ◽  
Justinn Renelies-Hamilton ◽  
Per Kryger ◽  
Annette Bruun Jensen ◽  
Veronica M. Sinotte ◽  
...  

Agricultural and apicultural practices expose honeybees to a range of pesticides that have the potential to negatively affect their physiology, neurobiology, and behavior. Accumulating evidence suggests that these effects extend to the honeybee gut microbiome, which serves important functions for honeybee health. Here we test the potential effects of the pesticides thiacloprid, acetamiprid, and oxalic acid on the gut microbiota of honeybees, first in direct in vitro inhibition assays and secondly in an in vivo caged bee experiment to test if exposure leads to gut microbiota community changes. We found that thiacloprid did not inhibit the honeybee core gut bacteria in vitro, nor did it affect overall community composition or richness in vivo. Acetamiprid did also not inhibit bacterial growth in vitro, but it did affect community structure within bees. The eight bacterial genera tested showed variable levels of susceptibility to oxalic acid in vitro. In vivo, treatment with this pesticide reduced amplicon sequence variant (ASV) richness and affected gut microbiome composition, with most marked impact on the common crop bacteria Lactobacillus kunkeei and the genus Bombella. We conducted network analyses which captured known associations between bacterial members and illustrated the sensitivity of the microbiome to environmental stressors. Our findings point to risks of honeybee exposure to oxalic acid, which has been deemed safe for use in treatment against Varroa mites in honeybee colonies, and we advocate for more extensive assessment of the long-term effects that it may have on honeybee health.


mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Christian Diener ◽  
Sean M. Gibbons ◽  
Osbaldo Resendis-Antonio

ABSTRACT Compositional changes in the gut microbiota have been associated with a variety of medical conditions such as obesity, Crohn’s disease, and diabetes. However, connecting microbial community composition to ecosystem function remains a challenge. Here, we introduce MICOM, a customizable metabolic model of the human gut microbiome. By using a heuristic optimization approach based on L2 regularization, we were able to obtain a unique set of realistic growth rates that corresponded well with observed replication rates. We integrated adjustable dietary and taxon abundance constraints to generate personalized metabolic models for individual metagenomic samples. We applied MICOM to a balanced cohort of metagenomes from 186 people, including a metabolically healthy population and individuals with type 1 and type 2 diabetes. Model results showed that individual bacterial genera maintained conserved niche structures across humans, while the community-level production of short-chain fatty acids (SCFAs) was heterogeneous and highly individual specific. Model output revealed complex cross-feeding interactions that would be difficult to measure in vivo. Metabolic interaction networks differed somewhat consistently between healthy and diabetic subjects. In particular, MICOM predicted reduced butyrate and propionate production in a diabetic cohort, with restoration of SCFA production profiles found in healthy subjects following metformin treatment. Overall, we found that changes in diet or taxon abundances have highly personalized effects. We believe MICOM can serve as a useful tool for generating mechanistic hypotheses for how diet and microbiome composition influence community function. All methods are implemented in an open-source Python package, which is available at https://github.com/micom-dev/micom. IMPORTANCE The bacterial communities that live within the human gut have been linked to health and disease. However, we are still just beginning to understand how those bacteria interact and what potential interventions to our gut microbiome can make us healthier. Here, we present a mathematical modeling framework (named MICOM) that can recapitulate the growth rates of diverse bacterial species in the gut and can simulate metabolic interactions within microbial communities. We show that MICOM can unravel the ecological rules that shape the microbial landscape in our gut and that a given dietary or probiotic intervention can have widely different effects in different people.


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