Metabolic cooperation among commensal bacteria supports Drosophila juvenile growth under nutritional stress

SUMMARYThe gut microbiota shapes animal growth trajectory in stressful nutritional environments, but the molecular mechanisms behind such physiological benefits remain poorly understood. The gut microbiota is mostly composed of bacteria, which construct metabolic networks among themselves and with the host. Until now, how the metabolic activities of the microbiota contribute to host juvenile growth remains unknown. Here, using Drosophila as a host model, we report that two of its major bacterial partners, Lactobacillus plantarum and Acetobacter pomorum engage in a beneficial metabolic dialogue that boosts host juvenile growth despite nutritional stress. We pinpoint that lactate, produced by L. plantarum, is utilized by A. pomorum as an additional carbon source, and A. pomorum provides essential amino-acids and vitamins to L. plantarum. Such bacterial cross-feeding provisions a set of anabolic metabolites to the host, which may foster host systemic growth despite poor nutrition.GRAPHICAL ABSTRACTHIGHLIGHTSL. plantarum feeds lactate to A. pomorumA. pomorum supplies essential amino acids and vitamins to L. plantarumMicrobiota metabolic dialogue boosts Drosophila’s larval growthLactate utilization by Acetobacter releases anabolic metabolites to larvae

Download Full-text

Dietary essential amino acids restore liver metabolism in ovariectomized mice via hepatic estrogen receptor α

Nature Communications ◽

10.1038/s41467-021-27272-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sara Della Torre ◽

Valeria Benedusi ◽

Giovanna Pepe ◽

Clara Meda ◽

Nicoletta Rizzi ◽

...

Keyword(s):

Amino Acids ◽

Estrogen Receptor ◽

Weight Gain ◽

Molecular Mechanisms ◽

Liver Lipid ◽

Essential Amino Acids ◽

Estrogen Receptor Α ◽

Metabolic Effects ◽

Ovariectomized Mice ◽

Dietary Treatments

AbstractIn female mammals, the cessation of ovarian functions is associated with significant metabolic alterations, weight gain, and increased susceptibility to a number of pathologies associated with ageing. The molecular mechanisms triggering these systemic events are unknown because most tissues are responsive to lowered circulating sex steroids. As it has been demonstrated that isoform alpha of the estrogen receptor (ERα) may be activated by both estrogens and amino acids, we test the metabolic effects of a diet enriched in specific amino acids in ovariectomized (OVX) mice. This diet is able to block the OVX-induced weight gain and fat deposition in the liver. The use of liver-specific ERα KO mice demonstrates that the hepatic ERα, through the control of liver lipid metabolism, has a key role in the systemic response to OVX. The study suggests that the liver ERα might be a valuable target for dietary treatments for the post-menopause.

Download Full-text

D-Alanine esterification of teichoic acids contributes to Lactobacillus plantarum mediated intestinal peptidase expression and Drosophila growth promotion upon chronic undernutrition

10.1101/098434 ◽

2017 ◽

Author(s):

Renata C. Matos ◽

Hugo Gervais ◽

Pauline Joncour ◽

Martin Schwarzer ◽

Benjamin Gillet ◽

...

Keyword(s):

Cell Wall ◽

Lactobacillus Plantarum ◽

Bacterial Cell ◽

Molecular Mechanisms ◽

Growth Promotion ◽

Bacterial Cell Wall ◽

List Type ◽

Juvenile Growth ◽

Teichoic Acids ◽

Chronic Undernutrition

SummaryThe microbial environment influence animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that upon chronic undernutrition, strains of Lactobacillus plantarum, a dominant commensal partner of Drosophila, promote host juvenile growth and maturation partly via enhanced expression of intestinal peptidases. By screening a transposon insertion library of Lactobacillus plantarum in gnotobiotic Drosophila larvae, we identify a bacterial cell wall modifying machinery encoded by the pbpX2-dltXABCD operon that is critical to enhance host digestive capabilities and promote growth and maturation. Deletion of this operon leads to bacterial cell wall alteration with a complete loss of teichoic acids D-alanylation. We thus conclude that teichoic acids modifications participate in commensal-host interactions and specifically, D-alanine esterification of teichoic acids contributes to optimal L. plantarum mediated intestinal peptidase expression and Drosophila juvenile growth upon chronic undernutrition.Highlights- LpNC8 mutant library screening identifies genes affecting Drosophila growth promotion.- pbpX2-dlt operon is required for D-alanylation of teichoic acids and Drosophila growth.- Deleting the pbpX2-dlt operon alters host intestinal peptidase expression.- Peptidoglycan and pbpX2-dlt dependent signals are required for LpNC8 mediated growth promotion.eTOC blurbAnimals establish interactions with their microbial communities that shape many aspects of their physiology including juvenile growth. However, the underlying molecular mechanisms are largely undefined. Matos et al. reveal that bacterial teichoic acids modifications contribute to host juvenile growth promotion.

Download Full-text

Commensal bacteria differentially shape the nutritional requirements of Drosophila during juvenile growth

10.1101/728774 ◽

2019 ◽

Author(s):

Jessika Consuegra ◽

Théodore Grenier ◽

Patrice Baa-Puyoulet ◽

Isabelle Rahioui ◽

Houssam Akherraz ◽

...

Keyword(s):

Gut Microbiota ◽

Large Scale ◽

Larval Growth ◽

Commensal Bacteria ◽

Nutritional Deficiencies ◽

Nutritional Requirements ◽

Juvenile Growth ◽

Bacterial Strains ◽

Metabolic Intermediate ◽

The Impact

AbstractThe interplay between nutrition and the microbial communities colonizing the gastro-intestinal tract (i.e. gut microbiota) determines juvenile growth trajectory. Nutritional deficiencies trigger developmental delays, and an immature gut microbiota is a hallmark of pathologies related to childhood undernutrition. However, how commensal bacteria modulate the impact of nutrition on juvenile growth remains elusive. Here, using gnotobiotic Drosophila melanogaster larvae independently associated with two model commensal bacterial strains, Acetobacter pomorumWJL (ApWJL) and Lactobacillus plantarumNC8 (LpNC8), we performed a large-scale, systematic nutritional screen based on larval growth in 40 different and precisely controlled nutritional environments. We combined these results with genome-based metabolic network reconstruction to define the biosynthetic capacities of Drosophila germ-free (GF) larvae and its two commensal bacteria. We first established that ApWJL and LpNC8 differentially fulfills the nutritional requirements of the ex-GF larvae and parsed such difference down to individual amino acids, vitamins, other micronutrients and trace metals. We found that Drosophila commensal bacteria not only fortify the host’s diet with essential nutrients but, in specific instances, functionally compensate for host auxotrophies, by either providing a metabolic intermediate or nutrient derivative to the host or by uptaking, concentrating and sparing contaminant traces of micronutrients. Our systematic work reveals that, beyond the molecular dialogue engaged between the host and its commensal partners, Drosophila and its facultative bacterial partners establish an integrated nutritional network relying on nutrients sparing and utilization.

Download Full-text

Manipulation of dietary amino acids prevents and reverses obesity in mice through multiple mechanisms that modulate energy homeostasis

10.2337/figshare.12771341.v1 ◽

2020 ◽

Author(s):

Ada Admin ◽

Chiara Ruocco ◽

Maurizio Ragni ◽

Fabio Rossi ◽

Pierluigi Carullo ◽

...

Keyword(s):

Amino Acids ◽

Energy Metabolism ◽

Energy Homeostasis ◽

Molecular Mechanisms ◽

Uncoupling Protein ◽

Essential Amino Acids ◽

Brown Fat ◽

Acid Oxidation ◽

White Fat

Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary and molecular mechanisms able to improve energy metabolism is of paramount medical importance, as such mechanisms can be leveraged as a therapy for obesity and related disorders. Here, <a>we show that a designer protein-deprived diet enriched in free essential amino acids can i) promote the brown fat thermogenic program and fatty acid oxidation, ii) stimulate uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white fat, iii) change the gut microbiota composition, and iv) prevent and reverse obesity and dysregulated glucose homeostasis in multiple mouse models, prolonging the healthy lifespan. </a>These effects are independent of unbalanced amino acid ratio, energy consumption, and intestinal calorie absorption. A brown fat-specific activation of the mechanistic target of rapamycin complex 1 seems involved in the diet-induced beneficial effects, as also strengthened by <i>in vitro</i> experiments. Hence, our results suggest that brown and white fat may be targets of specific amino acids to control UCP1-dependent and -independent thermogenesis, thereby contributing to the improvement of metabolic health.

Download Full-text

Amino acid limitation regulates gene expression

Proceedings of The Nutrition Society ◽

10.1017/s0029665199000828 ◽

1999 ◽

Vol 58 (3) ◽

pp. 625-632 ◽

Cited By ~ 29

Author(s):

Alain Bruhat ◽

Céline Jousse ◽

Pierre Fafournoux

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Amino Acid ◽

Molecular Mechanisms ◽

Binding Protein ◽

Regulation Of Gene Expression ◽

Essential Amino Acids ◽

Mrna Levels ◽

Dependent Manner ◽

Control Of Gene Expression

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

Download Full-text

Improving the levels of essential amino acids and sulfur metabolites in plants

Biological Chemistry ◽

10.1515/bc.2005.097 ◽

2005 ◽

Vol 386 (9) ◽

Cited By ~ 54

Author(s):

Gad Galili ◽

Rachel Amir ◽

Rainer Hoefgen ◽

Holger Hesse

Keyword(s):

Amino Acids ◽

Metabolic Engineering ◽

Amino Acid Metabolism ◽

Metabolic Networks ◽

Acid Metabolism ◽

Significant Proportion ◽

Essential Amino Acids ◽

Plant Foods ◽

Livestock Feeds ◽

Low Levels

AbstractPlants represent the major source of food for humans, either directly or indirectly through their use as livestock feeds. Plant foods are not nutritionally balanced because they contain low proportions of a number of essential metabolites, such as vitamins and amino acids, which humans and a significant proportion of their livestock cannot produce on their own. Among the essential amino acids needed in human diets, Lys, Met, Thr and Trp are considered as the most important because they are present in only low levels in plant foods. In the present review, we discuss approaches to improve the levels of the essential amino acids Lys and Met, as well as of sulfur metabolites, in plants using metabolic engineering approaches. We also focus on specific examples for which a deeper understanding of the regulation of metabolic networks in plants is needed for tailor-made improvements of amino acid metabolism with minimal interference in plant growth and productivity.

Download Full-text

Metabolic Cooperation among Commensal Bacteria Supports Drosophila Juvenile Growth under Nutritional Stress

iScience ◽

10.1016/j.isci.2020.101232 ◽

2020 ◽

Vol 23 (6) ◽

pp. 101232 ◽

Cited By ~ 2

Author(s):

Jessika Consuegra ◽

Théodore Grenier ◽

Houssam Akherraz ◽

Isabelle Rahioui ◽

Hugo Gervais ◽

...

Keyword(s):

Nutritional Stress ◽

Commensal Bacteria ◽

Juvenile Growth ◽

Metabolic Cooperation

Download Full-text

Mutually Beneficial Symbiosis Between Human and Gut-Dominant Bacteroides Species Through Bacterial Assimilation of Host Mucosubstances

10.1101/2020.08.21.262261 ◽

2020 ◽

Author(s):

Masahiro Sato ◽

Kanta Kajikawa ◽

Tomoya Kumon ◽

Daisuke Watanabe ◽

Ryuichi Takase ◽

...

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Health Promotion ◽

Gut Microbiota ◽

Human Health ◽

Short Chain Fatty Acids ◽

Essential Amino Acids ◽

Fasting State ◽

Human Gut ◽

Human Host

AbstractThe composition of gut microbiota is influenced by the quantity and type of nutrients in host. Even with some Bacteroides species being categorized as pathogens, Bacteroides is one of the most dominant gut bacteria. Here we indicate the physiological determinants of the species of Bacteroides for being dominant in human gut microbiota. Each of the host extracellular mucosubstances including glycosaminoglycans (GAGs) and mucin has grown human gut microbiota. In spite of the differences among initial microbiota profiles, Bacteroides species dominated the community when GAG (e.g., chondroitin sulfate or hyaluronan) was used as a sole carbon source. In fact, GAGs and the Bacteroides genes which are vital for the degradation of GAGs were commonly detected in human feces. Mucin has encouraged the growth of Bacteroides and several other genera. A comprehensive analysis on the degradation and assimilation of mucosubstances by the genus Bacteroides using around 30 species has shown that most species degrade and assimilate GAGs and mucin, showing that Bacteroides species can survive even in the undernutrition condition including the fasting state. In the assimilation of GAG or mucin, Bacteroides species significantly secreted essential amino acids, γ-amino butyrate (GABA), and/or short-chain fatty acids which are needed for human health. This is the first report as regards mutually beneficial interaction between human and Bacteroides species via bacterial assimilation of host mucosubstances and secretion of metabolites for host health promotion.SignificanceThe genus Bacteroides is one of the most dominant gut bacteria, although its beneficial effects on human health have not been well understood. Here, we show modes of action in human-Bacteroides interrelationship. Mucosubstances including GAGs and mucin secreted by human host are abundant in gut for microbiota to grow well. Bacteroides species are dominant in the community in the presence of GAGs, and provide human host with a considerable amount of essential amino acids, γ-amino butyrate, and short-chain fatty acids produced from mucosubstances. These results postulate mutually beneficial symbiosis system between human and Bacteroides through bacterial assimilation of host mucosubstances and secretion of metabolites for human body and mental health promotion even in the undernutrition condition including the fasting state.

Download Full-text

Essential amino acid provisioning by termite-associated gut microbiota

10.7287/peerj.preprints.1109 ◽

2015 ◽

Author(s):

Paul A Ayayee ◽

Susan C Jones ◽

Zakee L Sabree

Keyword(s):

Amino Acids ◽

Gut Microbiota ◽

Essential Amino Acid ◽

Isotope Analysis ◽

Essential Amino Acids ◽

Reticulitermes Flavipes ◽

Subterranean Termite ◽

Termite Gut ◽

Eastern Subterranean Termite ◽

Assimilable Nitrogen

Gut-associated microbes of many insects provide a variety of beneficial nutritive functions to their hosts such as the provisioning of essential amino acids (EAAs) to those that feed on diets limited in assimilable nitrogen (i.e., wood). We investigated this function by the gut microbiota of the eastern subterranean termite (Reticulitermes flavipes) using 13C-stable isotope analysis of EAAs in the diet and termite samples. Evidence of possible microbe input was revealed by 13C-depletion of termite carcass (-27.0 ± 0.43‰, mean ± s.e.), and termite gut filtrate samples (-27.3 ± 0.58‰) relative to their wood diet (-26.0 ± 0.48‰) (F (2, 63) = 6.2, P < 0.004). An investigation of the identity of non-dietary EAA sources determined that termites predominantly incorporated EAAs derived from bacteria, with minor fungal input. The most likely means of EAA acquisition is through proctodeal trophallaxis (mouth-anus feeding), a well-established feature of termite colony nestmates, and subsequent digestion of the microbial fraction in the transferred food. Our study provides empirical data in support of the gut microbial EAA provisioning function in termites by using 13C-stable isotopes to determine the microbial origins of incorporated EAAs in termite tissues.

Download Full-text