REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Purified anti-E. coli Crp	BioLegend	Cat# 664304; RRID: AB_2565553
Purified anti-E. coli RNA Sigma 70	BioLegend	Cat# 663202; RRID: AB_2564410
Goat anti-mouse IgG	Sigma-Aldrich	Cat# A0168; RRID: AB_257867
Bacterial and Virus Strains
E. coli: OP50	CGC	RRID:WB-STRAIN:OP50
E. coli: OP50-MR (metformin resistant)	Cabreiro et al., 2013	N/A
E. coli: OP50(xu363)	CGC	RRID:WB-STRAIN: OP50(xu363)
E. coli: OP50 ΔptsHΔptsIΔCrr::kan	Cynthia Kenyon (Lee et al., 2009)	N/A
Keio collection: Single-gene knockout mutants in E. coli BW25113 background	NBRP	https://shigen.nig.ac.jp/ecoli/strain/resource/keioCollection/list/
E. coli: OP50 ΔadiA::kan	This study	N/A
E. coli: OP50 ΔarcA::kan	This study	N/A
E. coli: OP50 ΔargG::kan	This study	N/A
E. coli: OP50 ΔargR::kan	This study	N/A
E. coli: OP50 ΔastA::kan	This study	N/A
E. coli: OP50 ΔcpdA::kan	This study	N/A
E. coli: OP50 Δcra::kan	This study	N/A
E. coli: OP50 Δcrp::kan	This study	N/A
E. coli: OP50 Δcrr::kan	This study	N/A
E. coli: OP50 ΔcsiR::kan	This study	N/A
E. coli: OP50 ΔcyaA::kan	This study	N/A
E. coli: OP50 Δfur::kan	This study	N/A
E. coli: OP50 ΔgcvA::kan	This study	N/A
E. coli: OP50 ΔgcvH::kan	This study	N/A
E. coli: OP50 ΔgcvP::kan	This study	N/A
E. coli: OP50 ΔgcvT::kan	This study	N/A
E. coli: OP50 ΔglpK::kan	This study	N/A
E. coli: OP50 Δhpt::kan	This study	N/A
E. coli: OP50 ΔmarA::kan	This study	N/A
E. coli: OP50 Δmlc::kan	This study	N/A
E. coli: OP50 Δnac::kan	This study	N/A
E. coli: OP50 ΔntrC::kan	This study	N/A
E. coli: OP50 ΔrbsK::kan	This study	N/A
E. coli: OP50 ΔspeA::kan	This study	N/A
E. coli: OP50 ΔspeB::kan	This study	N/A
E. coli: OP50 ΔspeF::kan	This study	N/A
E. coli: OP50 ΔtdcB::kan	This study	N/A
E. coli: OP50 ΔtdcC::kan	This study	N/A
E. coli: OP50 ΔcpdAΔcrp::kan	This study	N/A
E. coli: OP50 ΔcpdAΔcyaA::kan	This study	N/A
E. coli: OP50 ΔspeAΔadiA::kan	This study	N/A
E. coli: OP50 ΔspeAΔspeB::kan	This study	N/A
E. coli: OP50 ΔspeBΔastA::kan	This study	N/A
E. coli: OP50 ΔadiAΔastAΔspeA::kan	This study	N/A
E. coli: OP50 ΔadiAΔastAΔspeAΔspeB::kan	This study	N/A
E. coli: OP50 pCrp	This study	N/A
E. coli: OP50 pAstC	This study	N/A
E. coli: OP50 pFepA	This study	N/A
E. coli: OP50 pFucI	This study	N/A
E. coli: OP50 pGalF	This study	N/A
E. coli: OP50 pGapA	This study	N/A
E. coli: OP50 pMdh	This study	N/A
E. coli: OP50 pMntR	This study	N/A
E. coli: OP50 pOmpA	This study	N/A
E. coli: OP50 pSodA	This study	N/A
E. coli: OP50 pUbiF	This study	N/A
E. coli: OP50 pYdcS	This study	N/A
E. coli: OP50 pYbjJ	This study	N/A
E. coli: OP50 Δcrp::kan pCrp	This study	N/A
E. coli: OP50 ΔcyaA::kan pCrp	This study	N/A
Chemicals, Peptides, and Recombinant Proteins
5-Fluoro-2′-deoxyuridine 98+%	Alfa Aesar	Cat# L16497
Adenosine ≥ 99%	Sigma-Aldrich	Cat# A9251
Adenosine 3′,5′-cyclic monophosphate (cAMP)	Acros Organics	Cat# 225800010
Agmatine sulfate 97%	Alfa Aesar	Cat# H55363
Agar	Sigma-Aldrich	Cat# A7002
Bacto peptone	BD Biosciences	Cat# 211677
CHAPS	GE Healthcare	Cat# 17-1314-01
cOmplete protease inhibitor cocktail	Roche	Cat# 11697498001
D-(+)-Glucose ≥ 99.5%	Sigma-Aldrich	Cat# G8270
D-(−)-Ribose ≥ 99%	Sigma-Aldrich	Cat# R7500
Dithiothreitol (DTT)	GE Healthcare	Cat# 17-1318-01
Glycerol ≥ 99.5%	Thermo Fisher Scientific	Cat# BP229-1
Iodoacetamide (IAA)	Fluka	Cat# 57670
Isopropyl-β-D-thiogalactopyranoside (IPTG) ≥ 99%	Thermo Fisher Scientific	Cat# BP1755
L-Serine	Sigma-Aldrich	Cat# S4500
LB Broth Miller	Fisher BioReagents	Cat# BP1426
Lithium acetoacetate ≥ 90%	Sigma-Aldrich	Cat# A8509
Metformin (1,1-Dimethylbiguanide hydrochloride) ≥ 98%	LKT Laboratories	Cat# M2076
MRS broth	BD Difco	Cat# 288130
Perhexiline maleate salt ≥ 98%	Sigma-Aldrich	Cat# SML0120
Sequencing grade modified trypsin	Promega	Cat# V5111
Soy peptone	Sigma-Aldrich	Cat# P6713
Thiourea	Sigma-Aldrich	Cat# T8656
Tryptone	BD Biosciences	Cat# 211705
Urea	GE Healthcare	Cat# 17-1319-01
Yeast extract	BD Biosciences	Cat# 288620
Critical Commercial Assays
Biolog Phenotype Microarrays PM1, PM2A, PM3B, PM4A	Biolog	Cat# 12191
Biolog Dye mix A	Biolog	Cat# 74221
Clarity Western ECL Substrate	Bio-Rad	Cat# 1705060
CyDye DIGE Fluor Minimal Labeling Kit	GE Healthcare	Cat# 25-8010-65
Direct-zol RNase Miniprep Kit	Zymo Research	Cat# R2060
GenElute Plasmid Miniprep Kit	Sigma-Aldrich	Cat# PLN70
PlusOne Mini Dialysis Kit, 1kDa	GE Healthcare	Cat# 80648394
Qubit Protein Assay Kit	Thermo Fisher Scientific	Cat# Q33211
Qubit RNA HS Assay Kit	Thermo Fisher Scientific	Cat# Q32852
Quick Start Bradford Protein Assay Kit	Bio-Rad	Cat# 5000201
Deposited Data
C. elegans RNA-Seq reads and read counts.	This study	ArrayExpress: E-MTAB-7272
E. coli western blot images	This study	Mendeley Data https://data.mendeley.com/datasets/crmtpmd622/draft?a=ef347ccd-7532-44b0-8925-d2c04a71b419
C. elegans confocal microscopy images	This study	Mendeley Data https://data.mendeley.com/datasets/crmtpmd622/draft?a=ef347ccd-7532-44b0-8925-d2c04a71b419
C. elegans and D. melanogaster lifespan data	This study	Table S1
4-way screen data	This study	Table S2
E. coli proteomics data	This study	Table S3
E. coli metabolomics data	This study	Table S4
E. coli and human microbiota metabolic data	This study	Table S5
C. elegans RNA-seq data	This study	Table S6
C. elegans fatty acid metabolomics data	This study	Table S7
Kiel cohort data (16S rRNA gene sequencing)	This study	Available upon application from the PopGen biobank (https://www.uksh.de/p2n/Information+for+Researchers.html)
Spanish cohort data (metagenomics sequencing)	Wu et al., 2017	PRJNA361402
Swedish cohort data (metagenomics sequencing)	Forslund et al., 2015, Karlsson et al., 2013	PRJEB1786
Danish cohort data (metagenomics sequencing)	Le Chatelier et al., 2013	PRJEB5224 PRJEB1220 PRJEB4336 PRJEB2054
Mapped microbial abundances for metagenome-based cohort data	This study	Mendeley Data; https://data.mendeley.com/datasets/crmtpmd622/draft?a=ef347ccd-7532-44b0-8925-d2c04a71b419
Refined AGORA models with agmatine transporters and extracellular agmatine production	This study	Mendeley Data; https://data.mendeley.com/datasets/crmtpmd622/draft?a=ef347ccd-7532-44b0-8925-d2c04a71b419
E. coli OP50 metabolic model	Zimmermann et al., 2019	N/A
Experimental Models: Organisms/Strains
C. elegans: N2 Bristol	CGC	CGC: 10570
C. elegans: STE68: nhr-49(nr2041) I	CGC	RRID:WB-STRAIN:STE68
C. elegans: BC11281: dpy-5(e907) I sEx11281[rCes R07H5.2::GFP + pCeh361]	CGC	RRID:WB-STRAIN:BC11281
C. elegans: BX113: lin-15B&lin-15A(n765) X, waEx15[Pfat-7::GFP + lin15(+)]	CGC	RRID:WB-STRAIN:BX113
C. elegans: BC12124: sEx12124[R08H2.1::GFP]	CGC	RRID:WB-STRAIN:BC12124
C. elegans: VS10: hjIs37[Pvha-6::mRFP-PTS1 + Cbr- unc-119(+)]	CGC	RRID:WB-STRAIN:VS10
C. elegans: LIU1: ldrIs1[Pdhs-3::dhs-3::GFP + unc-76(+)]	CGC	RRID:WB-STRAIN:LIU1
C. elegans: CW152: gas-1(fc21) X	CGC	RRID:WB-STRAIN: CW152
C. elegans: CU5991: fzo-1(tm1133) II	CGC	RRID:WB-STRAIN: CU5991
C. elegans: VC1785: F08A8.1(ok2257) I	CGC	RRID:WB-STRAIN: VC1785
C. elegans: RB1985: C48B4.1(ok2619) III	CGC	RRID:WB-STRAIN: RB1985
C. elegans: MH5239: prx-5(ku517) II	CGC	RRID:WB-STRAIN: MH5239
C. elegans: CU6372: drp-1(tm1108) IV	CGC	RRID:WB-STRAIN: CU6372
C. elegans: CU5991: fzo-1(tm1133) II,	CGC	RRID:WB-STRAIN: CU5991
C. elegans: DA631: eat-3(ad426) II; him-8(e1489) IV	CGC	RRID:WB-STRAIN: DA631
C. elegans: MQ887: isp-1(qm150) IV	CGC	RRID:WB-STRAIN: MQ887
C. elegans: MAH547: sqEx82[Pargk-1::GFP+rol-6(su1006)]	CGC	RRID:WB-STRAIN:MAH547
C. elegans: LB54: nuo-1(ua-1) II, unc-119(ed3) III, uaEx25[p016bA352V], uaEx32[pDP#SU006, pTG96, pPD118.25NEO]	Bernard Lemire (DeCorby et al., 2007)	N/A
C. elegans: WBM392: wbmIs33[Pacs-2::GFP+rol-6(su1006)]	William Mair	N/A
C. elegans: SSR896: ssrIs496[Patgl1::GFP+rol-6(su1006)]	Supriya Srinivasan (Hussey et al., 2017)	N/A
C. elegans: MGH249: alxIs19[PCeACAD10::CeACAD10::mRFP3-HA Pmyo-2::GFP] 8X	Alexander Soukas (Wu et al., 2016)	N/A
C. elegans: GA641: wuIs177[Pftn-1::GFP+lin-15(+)]	David Gems (Ackerman and Gems, 2012)	N/A
C. elegans: FGC59: nhr-49(nr2041) I, wbmEx57[Pacs-2::GFP+rol-6(su1006)]	This study (Burkewitz et al., 2015)	N/A
C. elegans: FGC54: fgcIs1[Pcpt-5:: GFP+rol-6(su1006)]	This study	N/A
C. elegans: FGC45: ijIs10[unc-76(+)+Pcpr-5::GFP::lacZ]	This study and CGC	RRID:WB-STRAIN: IA123
C. elegans: FGC42: nIs470(Pcysl-2::GFP+Pmyo-2::mCherry]	This study and Robert Horvitz (Ma et al., 2012)	N/A
Drosophila melanogaster: white Dahomey (wDah) WT	Linda Partridge	N/A
Oligonucleotides
For information regarding oligonucleotide sequences used in this study please refer to Table S8.	This Study	Table S8
Recombinant DNA
Ahringer C. elegans RNAi library: RNAi control plasmid: pL4440	Source BioScience	http://www.sourcebioscience.com/products/life-science-research/clones/rnai-resources/c-elegans-rnai-collection-ahringer/
Ahringer C. elegans RNAi library: RNAi acs-1 knockdown: pL4440-acs-1	Source BioScience	http://www.sourcebioscience.com/products/life-science-research/clones/rnai-resources/c-elegans-rnai-collection-ahringer/
Ahringer C. elegans RNAi library: RNAi cco-1 knockdown: pL4440-cco-1	Source BioScience	http://www.sourcebioscience.com/products/life-science-research/clones/rnai-resources/c-elegans-rnai-collection-ahringer/
Vidal C. elegans RNAi library: RNAi OXCT-1/C05C10.3 knockdown: pL4440- OXCT-1/C05C10.3	Source BioScience	http://www.sourcebioscience.com/products/life-science-research/clones/rnai-resources/c-elegans-orf-rnai-resource-vidal/
ASKA collection E. coli ORF clones (GFP -): Crp overexpression: pCrp	NBRP	https://shigen.nig.ac.jp/ecoli/strain/resource/askaClone/list/ASKA_CLONE_MINUS
pCP20	CGSC	CGSC: 7629
pKD4	Datsenko and Wanner, 2000	Addgene Cat# 45605
pKD46	CGSC	CGSC: 7739
pPD95.75	Hilbert and Kim, 2018	Addgene Cat# 1494
Software and Algorithms
HISAT2 (v2.05)	Kim et al., 2015	https://ccb.jhu.edu/software/hisat2/index.shtml
R (v3.5.0)	R Core Team	https://www.r-project.org
edgeR (v3.22.0)	Robinson et al., 2010	https://bioconductor.org/packages/release/bioc/html/edgeR.html
DeCyder 7.0	GE Healthcare	Cat# 11505804
DESeq2	Love et al., 2014	https://bioconductor.org/packages/release/bioc/html/DESeq2.html
lme4 (v1.1-19)	https://cran.r-project.org/web/packages/lme4/index.html	https://cran.r-project.org/web/packages/lme4/index.html
Sybil (v2.0.4),	Gelius-Dietrich et al., 2013	https://cran.r-project.org/web/packages/sybil/index.html
cutadapt (v1.12)	10.14806/ej.17.1.200	https://cutadapt.readthedocs.io/en/stable/
prinseq lite (v0.20.4)	Schmieder and Edwards, 2011	http://prinseq.sourceforge.net/
Samtools (v1.4)	Li et al., 2009	http://www.htslib.org/
Peaks 7.5	Bioinformatics Solutions	http://www.bioinfor.com/peaks-studio-7-5-release/
Python (v2.7.13)	Python Core Team	https://www.python.org
GraphPad Prism 6	GraphPad Software	https://www.graphpad.com/scientific-software/prism/
JMP 12	SAS Institute	https://www.jmp.com/en_be/software/data-analysis-software.html