Biology subjects

Rabinowitz, J.

Publications and source records attributed to Rabinowitz, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Mapping the mammalian dark metabolome by in vivo isotope tracing

Despite decades of biochemical study, a comprehensive map of the mammalian metabolome remains elusive. Mass spectrometry-based metabolomics detects thousands of small molecule-associated signals in mammalian tissues, but it is currently unclear how many of these reflect products of endogenous metabolism. Here, we leverage systematic in vivo isotope tracing to infer the biosynthetic origins of unidentified metabolites. We administered 26 different isotopically labelled nutrients to mice, measured circulating and tissue metabolite labelling by mass spectrometry, and developed a statistical framework to infer the number of carbon atoms incorporated from each of these precursors into more than 4,000 putative metabolites. We show this information can be harnessed for biosynthesis-aware structure elucidation using a multimodal AI model that co-embeds isotopic labelling patterns with chemical structures. This approach revealed several previously unrecognized families of mammalian metabolites, including cysteine-derived alkylthiazolidines, dithioacetal mercapturic acid derivatives, short-chain N-acyltaurines, acylglycyltaurines, and N-oxidized taurines. It further uncovered a family of mevalonate-derived isoprenoid metabolites that includes 2,3-dihydrofarnesoic acid, which is markedly depleted in both mouse and human aging. Age-related depletion of these isoprenoids is driven by impaired coenzyme A synthesis. Our work establishes the biosynthetic precursors for thousands of unidentified metabolites and reveals multiple previously unrecognized branches of mammalian metabolism.

biochemistry↗

bioRxiv2026

Toward Computationally Complete Spatial Omics

Multimodal spatial omics has transformed biology by mapping molecular complexity within intact tissues, yet current technologies remain limited in the number of modalities measured simultaneously and often produce lower-quality data than single-modality assays. We present COSIE, a computational framework that generates high-resolution, multilayered molecular landscapes across tissue sections, individuals, and platforms. COSIE integrates histology, epigenome, transcriptome, proteome, and metabolome into a unified representation. Applied to 12 datasets spanning 10 spatial technologies, eight modalities, and nine tissue types, ranging from thousands of spots to millions of cells, COSIE outperforms existing methods. It resolves tissue structures, enhances noisy measurements, predicts unmeasured modalities, and captures dynamic processes. In human tumors, COSIE identifies invasive subregions linked to clinical outcomes and predicts spatial gene expression in TCGA samples using only histology images. By transforming fragmented data into comprehensive spatial maps, COSIE advances computationally complete spatial omics and the creation of digital tissue twins for biomedicine.

genomics↗

bioRxiv2025

AKT signaling in hepatocytes rapidly increases glucose phosphorylation and contribution to glycogen without affecting metabolite pool sizes or glycogen breakdown

Background and aimsHepatic insulin action is essential for whole body glucose homeostasis. Insulins inhibition of glycogen breakdown, suppression of gluconeogenesis, and activation of glycogen synthesis are critical for postprandial glucose disposal. AKT, a serine-threonine kinase and well-established insulin signaling target, regulates hepatic glucose metabolism through transcriptional and posttranslational mechanisms. However, current knowledge about AKTs regulation of hepatic glucose metabolism largely stems from genetic loss of function models, precluding observation of rapid, transcription-independent effects. MethodsStable isotope tracing using [U-13C]-glucose was coupled with pharmacological inhibition of AKT using MK-2206 in primary rat hepatocytes. Bulk metabolomics was performed on AKT knockout livers and primary rat hepatocytes treated with MK-2206. Radiolabeled glucose was used to quantify short-term changes to glycogen synthesis. ResultsMK-2206 treatment decreased glucose contribution to glucose 6-phosphate and uridine diphosphate glucose within minutes without significantly affecting total metabolite pool sizes or changes to glucokinase protein levels. This was accompanied by a decrease in glucose contribution to glycogen, independent of changes to glycogen breakdown or glycogen synthase phosphorylation. ConclusionsTogether, these results demonstrate that AKT acutely regulates glucose contribution to glycogen and its upstream precursors, suggesting a transcription-independent, glucokinase-centered mechanism for glycogen synthesis through the direct pathway.

cell biology↗

bioRxiv2025

Competitive catabolism in systemic mammalian metabolic homeostasis

Systemic metabolic homeostasis maintains circulating nutrient concentrations within physiological ranges. Insulin is central to this process, lowering circulating levels of glucose, free fatty acids, and ketones. Yet, how simultaneous homeostasis of these nutrients is achieved remains unclear. Here we develop a differential equation model of fasting metabolic homeostasis. Grounded in mass action kinetics, this multi-nutrient model reveals how a fixed energy demand naturally leads to competition between major circulating nutrients for oxidation ( competitive catabolism). Perturbative nutrient infusions confirm this emergent behavior. The multi-nutrient model predicts that insulin promotes fasting glucose homeostasis primarily indirectly by slowing lipolysis. It further identifies a physiological circuit by which obesity causes diabetes: Increased fat mass promotes lipolysis, releasing fatty acids into circulation that compete with glucose for oxidation, elevating glucose. Resulting hyperinsulinemia restores proper lipid catabolic flux but not euglycemia. Thus, quantitative modeling reveals a physiological homeostatic circuit through which obesity causes type 2 diabetes.

physiology↗

bioRxiv2025

Engineering auxin degradation into root-associated bacteria promotes plant growth

Overproduction of indole-3-acetic acid (IAA) by rhizosphere bacteria disrupts plant auxin homeostasis and induces root growth inhibition (RGI). Variovorax reverses this effect by degrading IAA, but the underlying pathway remains incompletely resolved. Here, using genetics, metabolomics, and isotope tracing, we define a nine-gene region (iadCDEFGHIJK2) required for IAA catabolism in Variovorax paradoxus CL014, identify a previously uncharacterized intermediate (CHNO), and revise the early oxidative steps of the pathway. Although IadDE adopts a Rieske-type oxygenase architecture, our data are consistent with the IadCDE complex functioning as a monooxygenase during IAA degradation. Using these insights, we introduce iad genes into two rhizobacterial chassis, Polaromonas MF047 and Paraburkholderia MF376. These engineered strains degrade IAA and alleviate RGI induced by exogenous IAA, an auxin-producing strain, and a synthetic bacterial community. Engineered Paraburkholderia MF376 delivers the strongest performance, improving plant growth in natural soil. Together, these results establish a framework for engineering auxin-balancing root commensals.

microbiology↗

bioRxiv2025

Many circulating indole and phenol metabolites are host derived

Indole and phenol metabolites are typically thought to be products of bacterial digestion of tryptophan (indoles) and phenylalanine or tyrosine (phenols). Interest in controlling gut microbial production of these metabolites has continually grown as they have important physiological impacts, with indoles agonizing AhR signaling, and phenols being associated with healthy body weight. While there is a growing wealth of research into which bacteria produce these metabolites, host contribution to their circulating pools has not been adequately characterized. Here, through stable isotope tracing in cell culture and mice, we show that mammalian cells can make aryl-pyruvates, -lactates, -acetates, and -carboxylic acids. Levels of these metabolites in mice and human patients are insensitive to perturbations of the microbiome. In contrast, bacterial metabolism is required to synthesize aryl-propionates and free indole, phenol, and cresol. Overall, we show that host metabolism is a primary contributor to circulating indole and phenol metabolite pools.

molecular biology↗

bioRxiv2025

Microengineered transplantation of human solid tumors for in vitro studies of CAR T immunotherapy

Treatment of solid malignancies using chimeric antigen receptor (CAR) T cells remains a significant challenge, but current efforts to advance this therapy are challenged by our limited capacity to probe and understand cancer-immune interactions in human solid tumors. Here, we present a microengineered platform for in vitro modeling of malignant solid tumors during CAR T therapy. This system makes it possible to vascularize human tumor explants and perfuse them with blood-borne immune cells in a controlled manner. We first present a microphysiological model of human lung adenocarcinomas infused with CAR-T cells and show how this system can be used to simulate, visualize, and interrogate tumor-directed trafficking and effector function of CAR T cells. We then demonstrate the proof-of-principle of testing a chemokine-directed CAR T cell engineering strategy in a model of malignant pleural mesothelioma and validating our in vitro assessment using a matching in vivo mouse model. Finally, we describe a potential therapeutic target discovered by single-cell RNA sequencing that can be pharmacologically modulated to increase the efficacy of CAR T cells for lung adenocarcinoma, for which we also present specific biomarkers identified by global metabolomics analysis. We believe that the bioengineering principle demonstrated here will make important contributions to developing new capabilities for preclinical studies of adoptive cell therapies for cancer and other complex diseases.

bioengineering↗

bioRxiv2025

Autophagy Suppresses CCL2 to Preserve Appetite and Prevent Lethal Cachexia

Macroautophagy (autophagy hereafter) captures intracellular components and delivers them to lysosomes for degradation and recycling1. In adult mice, autophagy sustains metabolism to prevent wasting by cachexia and to survive fasting, and also suppresses inflammation, liver steatosis, neurodegeneration, and lethality2,3. Defects in autophagy contribute to metabolic, inflammatory and degenerative diseases, however, the specific mechanisms involved were unclear 4. Here we profiled metabolism and inflammation in adult mice with conditional, whole-body deficiency in an essential autophagy gene and found that autophagy deficiency altered fuel usage, and reduced ambulatory activity, energy expenditure, and food intake, and elevated circulating GDF15, CXCL10, and CCL2. While deletion of Gdf15 or Cxcl10 provided no or mild benefit, deletion of Ccl2 restored food intake, suppressed cachexia and rescued lethality of autophagy-deficient mice. To test if appetite suppression by CCL2 was responsible for lethal cachexia we performed single nucleus RNA sequencing of the hypothalamus, the center of appetite control in the brain. Notably, we found that autophagy deficiency was specifically toxic to PMCH and HCRT neurons that produce orexigenic neuropeptides that promote food intake, which was rescued by deficiency in CCL2. Finally, the restoration of food intake via leptin deficiency prevented lethal cachexia in autophagy-deficient mice. Our findings demonstrate a novel mechanism where autophagy prevents induction of a cachexia factor, CCL2, which damages neurons that maintain appetite, the destruction of which may be central to degenerative wasting conditions. Key points of paper1) Autophagy-deficient mice have reduced food intake, systemic inflammation, and cachexia 2) CCL2, but not GDF15 or CXCL10, induces lethal cachexia caused by autophagy defect 3) Autophagy-deficient mice have CCL2-dependent destruction of appetite-promoting neurons in the hypothalamus 4) Leptin deficiency restores appetite and rescues lethal cachexia in autophagy-deficient mice 5) Autophagy-deficient mice die from cachexia mediated by appetite loss 6) Degenerative conditions due to impaired autophagy are caused by the inflammatory response to the damage 7) Targeting CCL2 may be a viable approach to prevent degenerative wasting disorders

molecular biology↗

bioRxiv2025

PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma

PAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. Here we show that PAX3-FOXO1+ RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved in de novo pyrimidine synthesis, including dihydrofolate reductase (DHFR). Consequently, PAX3-FOXO1+ cells display increased sensitivity to inhibition of DHFR by the chemotherapeutic drug methotrexate, and this dependence is rescued by provision of pyrimidine nucleotides. Methotrexate treatment mimics the metabolic and transcriptional impact of PAX3-FOXO1 silencing, reducing expression of genes related to PAX3-FOXO1-driven malignant cell states. Accordingly, methotrexate treatment slows growth of multiple PAX3-FOXO1+ tumor xenograft models, but not fusion-negative counterparts. Taken together, these data demonstrate that PAX3-FOXO1 induces cell states characterized by altered pyrimidine dependence and nominate methotrexate as an addition to the current therapeutic arsenal for treatment of these malignant pediatric tumors.

cancer biology↗

bioRxiv2024

Systemic metabolic changes in acute and chronic lymphocytic choriomeningitis virus infection

Viral infection of cells leads to metabolic changes, but how viral infection changes whole-body and tissue metabolism in vivo has not been comprehensively studied. In particular, it is unknown how metabolism might be differentially affected by an acute infection that the immune system can successfully clear, compared to a chronic and persistent infection. Here we used metabolomics and isotope tracing to identify metabolic changes in mice infected with acute or chronic forms of lymphocytic choriomeningitis virus (LCMV) for three or eight days. Both types of infection alter metabolite levels in blood and tissues, including itaconate and thymidine. However, we observed more dramatic metabolite changes in the blood and tissues of mice with chronic LCMV infection compared to those with acute infection. Isotope tracing revealed that the contribution of both glucose and glutamine to the tricarboxylic acid (TCA) cycle increase in the spleen, liver, and kidneys of mice infected with chronic LCMV, while acute LCMV only increases the contribution of glutamine to the TCA cycle in the spleen. We found that whole-body turnover of both glutamine and thymidine increase during acute and chronic infection, whereas whole-body glucose turnover was surprisingly unchanged. Activated T cells in vitro produce thymidine and mice with T cell leukemia display elevated serum thymidine, nominating T lymphocytes as the source of thymidine in LCMV infection. In sum, we provide comprehensive measurements of whole-body and tissue metabolism in acute and chronic viral infection, and identify altered thymidine metabolism as a marker of viral infection.

immunology↗

bioRxiv2024

Sulfur Amino Acid Restriction Enhances Exercise Capacity in Mice by Boosting Fat Oxidation

Dietary restriction of the sulfur-containing amino acids methionine and cysteine (SAAR) improves body composition, enhances insulin sensitivity, and extends lifespan; benefits seen also with endurance exercise. Yet, the impact of SAAR on skeletal muscle remains largely unexplored. Here we demonstrate that one week of SAAR in sedentary, young, male mice increases endurance exercise capacity. Indirect calorimetry showed that SAAR increased lipid oxidation at rest and delayed the onset of carbohydrate utilization during exercise. Transcriptomic analysis revealed increased expression of genes involved in fatty acid catabolism especially in glycolytic muscle following SAAR. These findings were functionally supported by increased fatty acid circulatory turnover flux and muscle {beta}-oxidation. Reducing lipid uptake from circulation through endothelial cell (EC)-specific CD36 deletion attenuated the running phenotype. Mechanistically, VEGF-signaling inhibition prevented exercise increases following SAAR, without affecting angiogenesis, implicating noncanonical VEGF signaling and EC CD36-dependent fatty acid transport in regulating exercise capacity by influencing muscle substrate availability.

physiology↗

bioRxiv2024

Immune Checkpoint Blockade Delays Cancer and Extends Survival in Murine DNA Polymerase Mutator Syndromes

Mutations in polymerases Pold1 and Pole exonuclease domains in humans are associated with increased cancer incidence, elevated tumor mutation burden (TMB) and response to immune checkpoint blockade (ICB). Although ICB is approved for treatment of several cancers, not all tumors with elevated TMB respond. Here we generated Pold1 and Pole proofreading mutator mice and show that ICB treatment of mice with high TMB tumors did not improve survival as only a subset of tumors responded. Similarly, introducing the mutator alleles into mice with Kras/p53 lung cancer did not improve survival, however, passaging mutator tumor cells in vitro without immune editing caused rejection in immune-competent hosts, demonstrating the efficiency by which cells with antigenic mutations are eliminated. Finally, ICB treatment of mutator mice earlier, before observable tumors delayed cancer onset, improved survival, and selected for tumors without aneuploidy, suggesting the use of ICB in individuals at high risk for cancer prevention. HighlightsO_LIGermline somatic and conditional Pold1 and Pole exonuclease domain mutations in mice produce a mutator phenotype. C_LIO_LISpontaneous cancers arise in mutator mice that have genomic features comparable to human tumors with these mutations. C_LIO_LIICB treatment of mutator mice with tumors did not improve survival as only a subset of tumors respond. C_LIO_LIIntroduction of the mutator alleles into an autochthonous mouse lung cancer model also did not produce immunogenic tumors, whereas passaging mutator tumor cells in vitro caused immune rejection indicating efficient selection against antigenic mutations in vivo. C_LIO_LIProphylactic ICB treatment delayed cancer onset, improved survival, and selected for tumors with no aneuploidy. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/597960v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@6cd159org.highwire.dtl.DTLVardef@243fd1org.highwire.dtl.DTLVardef@1d9da6borg.highwire.dtl.DTLVardef@192be51_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

One-carbon unit supplementation fuels tumor-infiltrating T cells and augments checkpoint blockade

Nucleotides perform important metabolic functions, carrying energy and feeding nucleic acid synthesis. Here, we use isotope tracing-mass spectrometry to quantitate the contributions to purine nucleotides of salvage versus de novo synthesis. We further explore the impact of augmenting a key precursor for purine synthesis, one-carbon (1C) units. We show that tumors and tumor-infiltrating T cells (relative to splenic T cells) synthesize purines de novo. Purine synthesis requires two 1C units, which come from serine catabolism and circulating formate. Shortage of 1C units is a potential bottleneck for anti-tumor immunity. Elevating circulating formate drives its usage by tumor-infiltrating T cells. Orally administered methanol functions as a formate pro-drug, with deuteration enabling control of formate-production kinetics. In MC38 tumors, safe doses of methanol raise formate levels and augment anti-PD-1 checkpoint blockade, tripling durable regressions. Thus, 1C deficiency can gate antitumor immunity and this metabolic checkpoint can be overcome with pharmacological 1C supplementation. Statement of significanceCheckpoint blockade has revolutionized cancer therapy. Durable tumor control, however, is achieved in only a minority of patients. We show that the efficacy of anti-PD-1 blockade can be enhanced by metabolic supplementation with one-carbon donors. Such donors support nucleotide synthesis in tumor-infiltrating T cells and merit future clinical evaluation.

immunology↗

bioRxiv2023

An end-to-end pipeline for succinic acid production at an industrially relevant scale using Issatchenkia orientalis

As one of the top value-added chemicals, succinic acid has been the focus of numerous metabolic engineering campaigns since the 1990s. However, microbial production of succinic acid at an industrially relevant scale has been hindered by high downstream processing costs arising from neutral pH fermentation. Here we describe the metabolic engineering of Issatchenkia orientalis, a non-conventional yeast with superior tolerance to highly acidic conditions, for cost-effective succinic acid production. Through deletion of byproduct pathways, transport engineering, and expanding the substrate scope, the resulting strains could produce succinic acid at the highest titers in sugar-based media at low pH (pH 3) in fed-batch fermentations using bench-top reactors, i.e. 109.5 g/L in minimal medium and 104.6 g/L in sugarcane juice medium. We further performed batch fermentation in a pilot-scale fermenter with a scaling factor of 300x, achieving 63.1 g/L of succinic acid using sugarcane juice medium. A downstream processing comprising of two-stage vacuum distillation and crystallization enabled direct recovery of succinic acid, without further acidification of fermentation broth, with an overall yield of 64.0%. Finally, we simulated an end-to-end low-pH succinic acid production pipeline, and techno-economic analysis and life cycle assessment indicate our process is financially viable and can reduce life cycle greenhouse gas emissions by 34-90% relative to fossil-based production processes. We expect I. orientalis can serve as a general industrial platform for the production of a wide variety of organic acids.

synthetic biology↗

bioRxiv2023

Targeting sterol regulatory element binding proteins (SREBPs) activation lowers intraocular pressure by halting its mechanosensing function in the trabecular meshwork

Trabecular meshwork (TM) cells are highly contractile and mechanosensitive to aid in maintaining intraocular pressure (IOP) homeostasis. Lipids are attributed to modulating TM contractility with poor mechanistic understanding. In this study using human TM cells, we identify the mechanosensing role of the transcription factors sterol regulatory element binding proteins (SREBPs) involved in lipogenesis. By constitutively activating SREBPs and pharmacologically inactivating SREBPs, we have mechanistically deciphered the attributes of SREBPs in regulating the contractile properties of TM. The pharmacological inhibition of SREBPs by fatostatin and molecular inactivation of SREBPs ex vivo and in vivo respectively results in significant IOP lowering. As a proof of concept, fatostatin significantly decreased the SREBPs responsive genes and enzymes involved in lipogenic pathways as well as the levels of the phospholipid, cholesterol, and triglyceride. Further, we show that fatostatin mitigated actin polymerization machinery and stabilization, and decreased ECM synthesis and secretion. We thus postulate that lowering lipogenesis in the TM outflow pathway can hold the key to lowering IOP by modifying the TM biomechanics. SynopsisIn this study, we show the role of lipogenic transcription factors sterol regulatory element binding proteins (SREBPs) in the regulation of intraocular pressure (IOP). (Synopsis Figure - Created using Biorender.com) O_LISREBPs are involved in the sensing of changes in mechanical stress on the trabecular meshwork (TM). SREBPs aid in transducing the mechanical signals to induce actin polymerization and filopodia/lamellipodia formation. C_LIO_LISREBPs inactivation lowered genes and enzymes involved in lipogenesis and modified lipid levels in TM. C_LIO_LISREBPs activity is a critical regulator of ECM engagement to the matrix sites. C_LIO_LIInactivation of SCAP-SREBP pathway lowered IOP via actin relaxation and decreasing ECM production and deposition in TM outflow pathway signifying a novel relationship between SREBP activation status and achieving IOP homeostasis. C_LI

cell biology↗

bioRxiv2023

Glycine homeostasis requires reverse SHMT flux

SUMMARYThe folate-dependent enzyme serine hydroxymethyltransferase (SHMT) reversibly converts serine into glycine and a tetrahydrofolate-bound one-carbon unit. Such one-carbon unit production plays a critical role in development, the immune system, and cancer. Here we show that the whole-body SHMT flux acts to net consume rather than produce glycine. Pharmacological inhibition of whole-body SHMT1/2 and genetic knockout of liver SHMT2 elevated circulating glycine levels up to eight-fold. Stable isotope tracing revealed that the liver converts glycine to serine, which is then converted by serine dehydratase into pyruvate and burned in the tricarboxylic acid cycle. In response to diets deficient in serine and glycine, de novo biosynthetic flux was unaltered but SHMT2- and serine dehydratase-mediated catabolic flux was lower. Thus, glucose-derived serine synthesis does not respond to systemic demand. Instead, circulating serine and glycine homeostasis is maintained through variable consumption, with liver SHMT2 as a major glycine-consuming enzyme.

biochemistry↗

bioRxiv2022

Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with [≤]5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.

genetics↗

bioRxiv2022

Gut bacterial nutrient preferences quantified in vivo

Great progress has been made in understanding gut microbiomes products and their effects on health and disease. Less attention, however, has been given to the inputs that gut bacteria consume. Here we quantitatively examine inputs and outputs of the mouse gut microbiome, using isotope tracing. The main input to microbial carbohydrate fermentation is dietary fiber, and to branched-chain fatty acids and aromatic metabolites is dietary protein. In addition, circulating host lactate, 3-hydroxybutyrate and urea (but not glucose or amino acids) feed the gut microbiome. To determine nutrient preferences across bacteria, we traced into genus-specific bacterial protein sequences. We find systematic differences in nutrient use: Most genera in the phylum Firmicutes prefer dietary protein, Bacteroides dietary fiber, and Akkermansia circulating host lactate. Such preferences correlate with microbiome composition changes in response to dietary modifications. Thus, diet shapes the microbiome by promoting the growth of bacteria that preferentially use the ingested nutrients.

molecular biology↗