Host Metabolic Responses Research Articles

Seeing the unseen: illuminating Toxoplasma gondii's metabolic manipulation.

Intracellular infection by a pathogen induces significant rewiring of host cell signaling and biological processes. Understanding how an intracellular pathogen such as Toxoplasma gondii modulates host cell metabolism with single-cell resolution has been challenged by the variability of infection within cultures and difficulties in separating host and parasite metabolic processes. A new study from Gallego-Lopez and colleagues (G. M. Gallego-López, E. C. Guzman, D. E. Desa, L. J. Knoll, M. C. Skala, mBio e00727-24, 2024, https://doi.org/10.1128/mbio.00727-24) applies a quantitative imaging approach to evaluate the host cell metabolism during intracellular infection with Toxoplasma. This study provides important insights into host metabolic responses to Toxoplasma infection and offers a valuable tool to dissect the mechanisms underlying parasite infection and pathophysiology.

Gut microbiota mediates the anti-inflammatory effects of supplemental infrared irradiation in mice.

In recent years, studies have shown that low-dose supplemental infrared (IR) irradiation exhibits systemic anti-inflammatory effects. The gut microbiota is increasingly recognized as a potential mediator of these effects due to its role in regulating host metabolism and inflammatory responses. To investigate the role of gut microbiota diversity and metabolite changes in the mechanism of light-emitting diodes (LED) infrared's anti-inflammatory action, we conducted IR irradiation on mice. Serum inflammatory cytokines were measured using ELISA, and fecal samples were subjected to metagenomic, untargeted, and targeted metabolomic analyses. Our results demonstrated a significant increase in the anti-inflammatory cytokine IL-10 in the IR group, accompanied by a declining trend in pro-inflammatory cytokines. Gut microbiome analysis revealed distinct alterations in composition and functional genes between the groups, including the enrichment of beneficial bacteria like various species of Parabacteroides and Akkermansia muciniphila in the IR group. Notably, the IR group exhibited enrichment in carbohydrate metabolism pathways and a reduction in DNA damage and repair pathways. Furthermore, targeted metabolomic analysis highlighted a notable increase in short-chain fatty acids (SCFAs), including butyric acid and isobutyric acid, which positively correlated with the abundance of several beneficial bacteria. These findings suggest a potential interplay between gut microbiota-derived SCFAs and the anti-inflammatory response. In conclusion, our study provides comprehensive insights into the changes in gut microbiota species and functions associated with IR irradiation. Moreover, we emphasize the significance of altered SCFAs levels in the IR group, which may contribute to the observed anti-inflammatory effects. Our findings contribute valuable evidence supporting the role of low-dose infrared light irradiation as an anti-inflammatory therapy.

MicroRNA-144-3p Inhibits Host Lipid Catabolism and Autophagy by Targeting PPARα and ABCA1 During Mycobacterium Tuberculosis Infection.

MicroRNA-mediated metabolic reprogramming recently has been identified as an important strategy for Mycobacterium tuberculosis (Mtb) to evade host immune responses. However, it is unknown what role microRNA-144-3p (miR-144-3p) plays in cellular metabolism during Mtb infection. Here, we report the meaning of miR-144-3p-mediated lipid accumulation for Mtb-macrophage interplay. Mtb infection was shown to upregulate the expression of miR-144-3p in macrophages. By targeting peroxisome proliferator-activated receptor α (PPARα) and ATP-binding cassette transporter A1 (ABCA1), miR-144-3p overexpression promoted lipid accumulation and bacterial survival in Mtb-infected macrophages, while miR-144-3p inhibition had the opposite effect. Furthermore, reprogramming of host lipid metabolism by miR-144-3p suppressed autophagy in response to Mtb infection. Our findings uncover that miR-144-3p regulates host metabolism and immune responses to Mtb by targeting PPARα and ABCA1, suggesting a potential host-directed tuberculosis therapy by targeting the interface of miRNA and lipid metabolism.

Transcriptomic responses of rabbits to infections by precocious line and wild-type Eimeria media: revealing molecular signatures and pathway differences in liver and duodenum during the peak and terminal phases of oocyst production.

Eimeria media is a principal pathogen responsible for rabbit coccidiosis, targeting the rabbit's intestinal epithelial cells. This parasitism damages the intestinal mucosal barrier, initiating a systemic immune and inflammatory response that jeopardizes the sustainable growth of rabbit farming. To understand the implications of infection on the host's immune and metabolic responses, we employed RNA-Seq to analyze RNA from the liver and duodenum tissues of post-infected rabbits infected with both the precocious line and wild-type strain of E.media. Comprehensive transcriptomic analysis revealed that the two parasites exhibit divergent transcriptomic imprints on host tissues. While the precocious line predominantly modulates immune-centric pathways with significant differential gene enrichment, wild-type strain favors pathways that affect metabolism. In addition, our study pinpointed a set of genes that undergo significant modifications in response to these effects. These revelations grant a fresh avenue to probe deeper into the symbiotic intricacies of the E.media and its rabbit host.

Modelling metabolic fluxes of tomato stems reveals that nitrogen shapes central metabolism for defence against Botrytis cinerea.

Among plant pathogens, the necrotrophic fungus Botrytis cinerea is one of the most prevalent, leading to severe crop damage. Studies related to its colonization of different plant species have reported variable host metabolic responses to infection. In tomato, high N availability leads to decreased susceptibility. Metabolic flux analysis can be used as an integrated method to better understand which metabolic adaptations lead to effective host defence and resistance. Here, we investigated the metabolic response of tomato infected by B. cinerea in symptomless stem tissues proximal to the lesions for 7 d post-inoculation, using a reconstructed metabolic model constrained by a large and consistent metabolic dataset acquired under four different N supplies. An overall comparison of 48 flux solution vectors of Botrytis- and mock-inoculated plants showed that fluxes were higher in Botrytis-inoculated plants, and the difference increased with a reduction in available N, accompanying an unexpected increase in radial growth. Despite higher fluxes, such as those involved in cell wall synthesis and other pathways, fluxes related to glycolysis, the tricarboxylic acid cycle, and amino acid and protein synthesis were limited under very low N, which might explain the enhanced susceptibility. Limiting starch synthesis and enhancing fluxes towards redox and specialized metabolism also contributed to defence independent of N supply.

Gut Microbiota and Its Implications for Cardiovascular Diseases – a Review

Background: The symbiotic relationship between the gut microbiota and cardiovascular health has become a main point in contemporary research, offering valuable insights into the pathogenesis of cardiovascular diseases (CVDs). This review aims to comprehensively examine the bidirectional communication between gut microbial communities and the cardiovascular system, explaining the intricate mechanisms that connect gut dysbiosis to the initiation and progression of CVDs.
 Material and Methods: A systematic literature review was conducted to compile and analyze relevant studies investigating the impact of the gut microbiota on cardiovascular health. Emphasis was placed on explaining the molecular and physiological mechanisms underlying the interaction between gut microbes and cardiovascular function.
 Results: Our review confirmed evidence linking gut microbiota-derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide and lipopolysaccharides to vascular function and inflammation. Additionally, we explored the modulation of host metabolism and immune responses by gut microbes, providing insights into their roles in atherosclerosis and hypertension. The review highlight the influence of diet and lifestyle on shaping the gut microbiome and, consequently, cardiovascular outcomes.
 Conclusions: Gut microbiota plays a crucial role in cardiovascular health and is involved in the start and development of various heart diseases. The identified molecular and physiological mechanisms highlight the need for complete understanding of the gut-cardiovascular axis. Moreover, the review emphasizes the potential of microbiota-targeted interventions, including probiotics and fecal microbiota transplantation, as innovative strategies for preventing and managing CVDs.

Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis

ABSTRACT Dysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD.

MTOR Signaling Pathway and Gut Microbiota in Various Disorders: Mechanisms and Potential Drugs in Pharmacotherapy.

The mammalian or mechanistic target of rapamycin (mTOR) integrates multiple intracellular and extracellular upstream signals involved in the regulation of anabolic and catabolic processes in cells and plays a key regulatory role in cell growth and metabolism. The activation of the mTOR signaling pathway has been reported to be associated with a wide range of human diseases. A growing number of in vivo and in vitro studies have demonstrated that gut microbes and their complex metabolites can regulate host metabolic and immune responses through the mTOR pathway and result in disorders of host physiological functions. In this review, we summarize the regulatory mechanisms of gut microbes and mTOR in different diseases and discuss the crosstalk between gut microbes and their metabolites and mTOR in disorders in the gastrointestinal tract, liver, heart, and other organs. We also discuss the promising application of multiple potential drugs that can adjust the gut microbiota and mTOR signaling pathways. Despite the limited findings between gut microbes and mTOR, elucidating their relationship may provide new clues for the prevention and treatment of various diseases.

Gut microbiome modulates the effects of a personalised postprandial-targeting (PPT) diet on cardiometabolic markers: a diet intervention in pre-diabetes

ObjectiveTo explore the interplay between dietary modifications, microbiome composition and host metabolic responses in a dietary intervention setting of a personalised postprandial-targeting (PPT) diet versus a Mediterranean (MED) diet in...

Does Obesity or Hyperglycemia Alter Metabolic Endotoxemia?

Obesity increases the risk of type 2 diabetes and non-alcoholic fatty liver disease, which are two interlinked diseases with a high health and economic burden. Obesogenic diets change the composition of intestinal microbes. Our objective is to move beyond associations of taxonomy and define specific microbial components that alter host immune and metabolic responses. Postbiotics are bacterial components or metabolites derived from living or dead bacteria that can modulate host immunity and metabolism. Lipopolysaccharide (LPS) is a classic example of a postbiotic that acts through toll-like receptor 4 (TLR4) to influence inflammation. Metabolic endotoxemia describes a chronic, low-level increase of LPS seen in blood during metabolic disease. However, it was recently shown that metabolic endotoxemia may be beneficial or detrimental to host metabolism depending on the type of LPS, which is dictated by different species of bacteria. It was previously unknown if obesity or hyperglycemia, is the main driver that alters metabolic endotoxemia. We hypothesized that obesity and hyperglycemia lead to an increase in the inflammatory properties of LPS found in the gut lumen and serum. We tested feces, and the systemic and portal serum obtained from mouse models of hyperglycemia (Akita+/- mice) and obesity ( ob/ob mice) for their TLR4 activation. It was found that hyperglycemia leads to increased fecal TLR4 activation, which can be reduced by lowering blood glucose in Akita+/- mice. In particular, a fed state promotes increased TLR4 activity in the serum of hyperglycemic mice. Elevated levels of TLR4 activity were observed in the serum of ob/ob mice. However, as these mice are transiently hyperglycemic, their elevated levels of blood glucose early on in their life may be a confounding factor leading to increased TLR4 activity. In conclusion, hyperglycemia is a main driver for metabolic endotoxemia and the increased inflammatory properties of LPS in the gut lumen. This research provides a framework of how specific metabolic disease characteristics influence inflammation and will help future studies looking to target the link between hyperglycemia and changes to the specific type of LPS. Canadian Institutes of Health Research, Farncombe Family Digestive Health and Research Institute This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Serum metabolomics combined with 16S rRNA sequencing to reveal the effects of Lycium barbarum polysaccharide on host metabolism and gut microbiota

Gut microbes and microbial metabolites derived from polysaccharides mediate beneficial effects related to polysaccharides consumption. Lycium barbarum polysaccharide (LBP) is the main bioactive components in L. barbarum fruits and possesses considerable health-promoting effects. In the present study, we aimed to investigate whether LBP supplementation influenced host metabolic responses and gut microbiota in healthy mice, and to identify bacterial taxa associated with the observed beneficial effects. Our results indicated that mice supplied with LBP at 200 mg/kg BW showed lower serum total cholesterol (TC), triglyceride (TG), and liver TG levels. LBP supplementation strengthened the antioxidant capacity of liver, supported the growth of Lactobacillus and Lactococcus, and stimulated short-chain fatty acids (SCFAs) production. Serum metabolomic analysis revealed that fatty acid degradation pathways were enriched, and RT-PCR further confirmed that LBP up-regulated the expression of liver genes involved in fatty acid oxidation. The Spearman’s correlation analysis indicated that some serum and liver lipid profiles and hepatic SOD activity were associated with Lactobacillus, Lactococcus, Ruminococcus, Allobaculum and AF12. Collectively, these findings provide new evidence for the potential preventive effect of LBP consumption on hyperlipidemia and nonalcoholic fatty liver disease.

A comparative analysis of gut microbial dysbiosis by select antibiotics and DSS to understand the effects of perturbation on the host immunity and metabolism

AimsBalanced gut microbial composition of the host plays a crucial role in maintaining harmony among various physiological processes to maintain physiological homeostasis. Immunity and metabolism are the two physiologies mainly controlled by the gut microbiota. Reports suggested that gut microbial composition and diversity alteration are the leading causes of the host's healthy homeostasis alteration or a diseased state. The extent of gut perturbation depends on the perturbing agents' strength, chemical nature, and mode of action. In the current report, we have studied the effects of different perturbing agents on gut microbial dysbiosis and its impact on host immunity and metabolism. Materials and methodsWe studied the perturbation of gut microbial composition and diversity using next-generation sequencing and further investigated the changes in host immune and metabolic responses. Key findingsEnrichment or abolition of a particular phylum or genus depended on the perturbing agents. In the current study, treatment with neomycin yielded an increase in the Bacteroidetes phylum. Vancomycin treatment caused a significant rise in Verrucomicrobia and Proteobacteria phyla. The treatment with AVNM and DSS caused a substantial increase in the Proteobacteria phylum. The gut microbial diversity was also lowest in AVNM treated group. The altered gut microbial composition ultimately altered the immune responses at localized and systemic levels of the host. Gut dysbiosis also changed the systemic level of SCFAs. SignificanceThis study will help us understand how the enrichment of a particular phylum and genus maintains the host's immune responses and metabolism.

Determining transcriptomic response of kidneys of olive flounder to viral hemorrhagic septicemia virus infection using next-generation sequencing

Viral hemorrhagic septicemia (VHS) in olive flounder (Paralichthys olivaceus) causes considerable economic losses in the flounder aquaculture industry in Korea. This study was aimed to identify the immune-associated genes contributing to VHSV infection progression in the kidneys of the olive flounder. Ten fish were divided into two groups via an intraperitoneal injection with either diethylpyrocarbonate-treated water or 106 50% tissue culture infective dose VHSV 100 μL−1 fish−1. At 24 h post-infection, kidney tissues were used for RNA sequencing to identify the differentially expressed genes (DEGs). The upregulated DEGs in the VHSV group included many genes linked to interleukins, chemokines, interferons and immune cell types. Functional enrichment analysis indicated that VHSV infection broadly affects the host metabolism and innate immune responses in the olive flounder. The present study provides a theoretical basis for the molecular mechanisms of VHSV that can be further explored in future studies.

Microbial dysbiosis and childhood asthma development: Integrated role of the airway and gut microbiome, environmental exposures, and host metabolic and immune response.

Asthma is a chronic and heterogeneous respiratory disease with many risk factors that typically originate during early childhood. A complex interplay between environmental factors and genetic predisposition is considered to shape the lung and gut microbiome in early life. The growing literature has identified that changes in the relative abundance of microbes (microbial dysbiosis) and reduced microbial diversity, as triggers of the airway-gut axis crosstalk dysregulation, are associated with asthma development. There are several mechanisms underlying microbial dysbiosis to childhood asthma development pathways. For example, a bacterial infection in the airway of infants can lead to the activation and/or dysregulation of inflammatory pathways that contribute to bronchoconstriction and bronchial hyperresponsiveness. In addition, gut microbial dysbiosis in infancy can affect immune development and differentiation, resulting in a suboptimal balance between innate and adaptive immunity. This evolving dysregulation of secretion of pro-inflammatory mediators has been associated with persistent airway inflammation and subsequent asthma development. In this review, we examine current evidence around associations between the airway and gut microbial dysbiosis with childhood asthma development. More specifically, this review focuses on discussing the integrated roles of environmental exposures, host metabolic and immune responses, airway and gut microbial dysbiosis in driving childhood asthma development.

Lead and copper led to the dysregulation of bile acid homeostasis by impairing intestinal absorption in Bufo gargarizans larvae: An integrated metabolomics and transcriptomics approach

Bile acids, as metabolic regulators and signaling molecules, play key roles in the regulation of host metabolism and immune responses. Heavy metals such as lead (Pb) and copper (Cu) are widespread environmental pollutants that threaten public health. However, the effects of heavy metals on bile acid metabolism and the underlying molecular mechanisms remain unclear, particularly for ecologically important amphibian species. In the present research, the effects of exposure to environmentally-relevant concentrations of Pb (250 μg/L), Cu (50 μg/L), and a mixture of both (Mix) on bile acid metabolism and the underlying molecular mechanisms in the intestines of Bufo gargarizans larvae were comprehensively investigated using histopathology, metabolomics and transcriptomics analysis. Our results suggested that Pb and/or Cu caused histopathological damage to the intestine and liver, such as decreased intestinal epithelial cell height and dilated hepatic sinusoid. The total bile acid level was decreased in the Pb and Mix exposure groups but elevated in the Cu treatment. A significant decrease in the ratio of conjugated to unconjugated bile acids was present in all treatment groups. Also, the level of GCA was increased while TCA and TCDCA were decreased in all exposure groups. In addition, exposure to Pb and Cu altered the expression levels of genes related to intestinal absorption. For example, mrp2, mrp3 and aqp4 had higher expression in the Pb and Mix treatment groups, and aqp1 and mrp4 were increased in the Cu treatment group. Overall, we speculated that the dysregulation of bile acid homeostasis induced by Pb and Cu exposure may be due to impaired intestinal absorption. These findings raise further concerns about the hazards of Pb and/or Cu in influencing bile acid metabolism that might lead to the development of metabolic diseases and inflammatory disorders.

Metabolic reprogramming and alteration of the redox state in hyper-productive MDCK cells for influenza a virus production

Influenza is a global public health issue leading to widespread morbidity and mortality with devastating economic loss annually. Madin-Darby Canine Kidney (MDCK) cell line has been a major cell line for influenza vaccine applications. Though many details of the host metabolic responses upon influenza A virus (IAV) infection have been documented, little is known about the metabolic reprogramming features of a hyper-productive host for IAV vaccine production. In this study, a MDCK cell clone H1 was shown to have a particular high productivity of 30 × 103 virions/cell. The glucose and amino acid metabolism of H1 were evaluated, indicating that the high producer had a particular metabolic reprogramming phenotype compared to its parental cell line (P): elevated glucose uptake, superior tricarboxylic acid cycle flux, moderate amino acid consumption, and better regulation of reactive oxygen species. Combined with the stronger mitochondrial function and mild antiviral and inflammatory responses characterized previously, our results indicated that the high producer had a sufficient intracellular energy supply, and balanced substrate distribution for IAV and host protein synthesis as well as the intracellular redox status. Understanding of these metabolic alterations paves the way for the rational cell line development and reasonable process optimization for high-yield influenza vaccine production.

Multi-omics analysis reveals the metabolic regulators of duodenal low-grade inflammation in a functional dyspepsia model.

Several gastrointestinal phenotypes and impairment of duodenal mucosal barrier have been reported in clinical studies in patients with functional dyspepsia (FD). Due to the preferential colonization of the mucosa, intestinal microbes and their metabolites are commonly involved in host metabolism and immune responses. However, there are no studies on the intertwined correlation among multi-level data. For more comprehensive illustrating, a multi-omics analysis focusing on the duodenum was performed in the FD rat model. We found that differential microbiomes in the duodenum were significantly correlated with the biosynthesis of lipopolysaccharide and peptidoglycan. The innate immune response-related genes, which were upregulated in the duodenum, were associated with the TLR2/TLR4-NFκB signaling pathway. More importantly, arachidonyl ethanolamide (anandamide, AEA) and endocannabinoid analogues showed linear relationships with the FD phenotypes. Taken together, multi-level data from microbiome, transcriptome and metabolome reveal that AEA may regulate duodenal low-grade inflammation in FD. These results suggest an important cue of gut microbiome–endocannabinoid system axis in the pathogenesis of FD.

Effects of integrated multi-trophic aquaculture on microbial communities, antibiotic resistance genes, and cultured species: A case study of four mariculture systems

Aquaculture is an important protein source in many countries, including China. Integrated multitrophic aquaculture (IMTA) is widely used to reduce the environmental pressure of aquaculture and to increase profits. However, effects of IMTA on host immune and metabolic responses, the dynamics of bacterial communities, and antibiotic resistance genes (ARGs) are relatively understudied. In this study, the IMTA mariculture systems with different combinations of the hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂), the whiteleg shrimp (Litopenaeus vannamei), and the alga (Gracilaria bailinae) were constructed to evaluate the effects of different culture systems on the aquatic environment and cultured species during the initial stage of aquaculture. Results showed that G. bailinae could effectively remove inorganic nutrients accumulated in water, which in turn significantly promoted growth and enhanced non-specific immunity and glycolipid metabolism in the hybrid grouper. Although ARGs were present throughout the culture process, the relative abundance of ARGs in three of the four culture systems decreased with culture time. This was especially the case in the monoculture and the fish-algal IMTA systems, indicating that these aquaculture systems had a scavenging effect on ARGs in the environment. Correlation and network analyses indicated that ARGs were not significantly correlated with environmental factors but were closely related to bacterial communities. Approximately 25 bacterial groups of Bacteroidetes and Proteobacteria were significantly correlated with ARGs, including aminoglycoside, beta-lactamase, chloramphenicol, and multidrug resistance genes. Moreover, tnpA-07, a transposase gene, indirectly affected ARGs through its interaction with Acteroidetes and Proteobacteria. This study provides insights into further optimizing culture methods and controlling the spread and ecological risk of ARGs in IMTA systems.

Machine learning and semi-targeted lipidomics identify distinct serum lipid signatures in hospitalized COVID-19-positive and COVID-19-negative patients

BackgroundLipids are involved in the interaction between viral infection and the host metabolic and immunological responses. Several studies comparing the lipidome of COVID-19-positive hospitalized patients vs. healthy subjects have already been reported. It is largely unknown, however, whether these differences are specific to this disease. The present study compared the lipidomic signature of hospitalized COVID-19-positive patients with that of healthy subjects, as well as with COVID-19-negative patients hospitalized for other infectious/inflammatory diseases. MethodsWe analyzed the lipidomic signature of 126 COVID-19-positive patients, 45 COVID-19-negative patients hospitalized with other infectious/inflammatory diseases and 50 healthy volunteers. A semi-targeted lipidomics analysis was performed using liquid chromatography coupled to mass spectrometry. Two-hundred and eighty-three lipid species were identified and quantified. Results were interpreted by machine learning tools. ResultsWe identified acylcarnitines, lysophosphatidylethanolamines, arachidonic acid and oxylipins as the most altered species in COVID-19-positive patients compared to healthy volunteers. However, we found similar alterations in COVID-19-negative patients who had other causes of inflammation. Conversely, lysophosphatidylcholine 22:6-sn2, phosphatidylcholine 36:1 and secondary bile acids were the parameters that had the greatest capacity to discriminate between COVID-19-positive and COVID-19-negative patients. ConclusionThis study shows that COVID-19 infection shares many lipid alterations with other infectious/inflammatory diseases, and which differentiate them from the healthy population. The most notable alterations were observed in oxylipins, while alterations in bile acids and glycerophospholipis best distinguished between COVID-19-positive and COVID-19-negative patients. Our results highlight the value of integrating lipidomics with machine learning algorithms to explore the pathophysiology of COVID-19 and, consequently, improve clinical decision making.

Gut-derived peptidoglycan remotely inhibits bacteria dependent activation of SREBP by Drosophila adipocytes.

Bacteria that colonize eukaryotic gut have profound influences on the physiology of their host. In Drosophila, many of these effects are mediated by adipocytes that combine immune and metabolic functions. We show here that enteric infection with some bacteria species triggers the activation of the SREBP lipogenic protein in surrounding enterocytes but also in remote fat body cells and in ovaries, an effect that requires insulin signaling. We demonstrate that by activating the NF-κB pathway, the cell wall peptidoglycan produced by the same gut bacteria remotely, and cell-autonomously, represses SREBP activation in adipocytes. We finally show that by reducing the level of peptidoglycan, the gut born PGRP-LB amidase balances host immune and metabolic responses of the fat body to gut-associated bacteria. In the absence of such modulation, uncontrolled immune pathway activation prevents SREBP activation and lipid production by the fat body.