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Table S8. identified by random forests analysis of shotgun sequencing data that exhibit significant differences in their representation in the fecal microbiomes between each two groups of mice.

(a) Species discriminating fecal microbiota of the Soil and Control mice. Mean importance of species identified by random forest are shown in the 5th column. Random forests assigns an importance score to each species by estimating the increase in error caused by removing that species from the set of predictors. In our analysis, we considered a species to be “highly predictive” if its importance score was at least 0.001. T-test was performed for the relative abundances of each species between the two groups of mice. P-values were at least 0.05 to be considered statistically significant.

Microbiological Random Forests Mean of relative abundance P-Value Species Microbiological Function (T-Test) Classification Bacterial Order Importance Score Soil Control Rhodococcus sp. 2G Engineered Corynebacteriales 0.002 5.73791E-05 1.9325E-05 9.3737E-06 Herminiimonas arsenitoxidans Engineered strain Bacteria 0.002 0.005112829 7.1580E-05 1.3995E-05 Aspergillus ibericus Engineered strain Fungi 0.002 0.001061181 9.2368E-05 7.3057E-05 Dichomitus squalens Engineered strain Fungi 0.002 0.018887472 8.0887E-05 4.1254E-05 sp. TTH0-4 Engineered strain Bacteria 0.001333333 0.025523638 2.2311E-05 8.2612E-06 Rhizobium tropici Engineered strain Bacteria Rhizobiales 0.001333333 0.02079554 7.0081E-05 4.2000E-05 Methylocystis bryophila Engineered strain Bacteria Rhizobiales 0.001333333 0.006513543 3.5401E-05 2.2044E-05 Alteromonas naphthalenivorans Engineered strain Bacteria Alteromonadales 0.001 0.000660472 2.0747E-05 4.6463E-05 Saccharomyces cerevisiae Engineered strain Fungi 0.001 0.002980726 3.9901E-05 7.3043E-05 Bacillus phage Belinda Antibiotic Phage 0.002 0.016409765 6.8789E-07 6.0681E-08 Streptomyces sp. Mg1 Antibiotic Bacteria 0.001333333 0.025944045 1.0137E-04 5.0762E-05 Streptosporangium sp. Antibiotic Bacteria Streptosporangiales 0.001333333 0.005225191 1.4746E-04 6.8699E-05 sp. Os17 Antibiotic Bacteria Pseudomonadales 0.001333333 0.019992445 4.0231E-05 1.3165E-05 Acanthamoeba castellanii Antibiotic Fungi 0.001 0.002183997 1.9172E-04 1.2956E-04 Pseudoalteromonas luteoviolacea Antibiotic Bacteria Alteromonadales 0.001333333 0.004368358 5.4894E-05 8.6223E-05 Pseudoalteromonas piscicida Antibiotic Bacteria Alteromonadales 0.001333333 0.003338405 4.6886E-05 8.2059E-05 Lactobacillus fermentum Antibiotic Bacteria Lactobacillales 0.001 0.025570099 1.9693E-04 4.6536E-04 sp. JP2-270 Antibiotic Bacteria Burkholderiales 0.001 0.001144007 4.0309E-05 9.2851E-05 Tetrapisispora phaffii Antibiotic Fungi 0.001 0.021789983 1.0335E-04 1.7016E-04 anisa Pathogany (no infecting mice) Bacteria 0.002333333 0.003555933 4.0114E-05 1.3879E-05 Scale drop disease virus Pathogany (no infecting mice) Bacteria 0.002333333 0.047897164 3.2350E-06 0.0000E+00 Pathogany (no infecting mice) Bacteria Burkholderiales 0.002 0.004001233 5.7584E-05 3.0745E-05 condimenti Pathogany (no infecting mice) Bacteria 0.001333333 0.013666952 3.3692E-05 1.4869E-05 Pathogany (no infecting mice) Bacteria 0.001333333 0.000588819 1.5019E-05 6.5443E-06 Rahnella aquatilis Pathogany (no infecting mice) Bacteria 0.001333333 0.029064014 6.8549E-05 4.3551E-05 Pathogany (no infecting mice) Bacteria Rhizobiales 0.001333333 0.004137196 8.4396E-06 1.1050E-06 Borrelia duttonii Pathogany (no infecting mice) Bacteria Borreliaceae 0.001333333 0.002099125 3.3756E-05 1.2974E-05 Pathogany (no infecting mice) Bacteria Bacillales 0.001 0.000562255 3.6211E-05 1.5288E-05 ulcerans Pathogany (no infecting mice) Bacteria Corynebacteriales 0.001 0.003869858 1.0380E-05 2.0078E-06 Pathogany (no infecting mice) Bacteria Enterobacterales 0.001 0.010304803 3.4115E-03 2.3240E-03 Lelliottia amnigena Pathogany (no infecting mice) Bacteria Enterobacterales 0.001 0.019044704 7.0061E-05 3.6456E-05 Pseudomonas oryzihabitans Pathogany (no infecting mice) Bacteria Pseudomonadales 0.001 0.002847013 2.8164E-05 2.0365E-05 insidiosa Pathogany (no infecting mice) Bacteria Burkholderiales 0.001 0.001367639 1.0216E-04 5.8764E-05 Parachlamydia acanthamoebae Pathogany (no infecting mice) Chlamydia 0.001 0.000544995 2.4367E-05 1.5029E-05 Leptospira alstonii Pathogany (no infecting mice) Bacteria Leptospiraceae 0.001 0.000830812 4.9841E-05 3.3563E-05 Plasmodium vinckei Pathogany (no infecting mice) Parasite 0.001 0.024245509 8.1069E-05 5.9239E-05 Cryptococcus neoformans Pathogany (no infecting mice) Fungi 0.001 0.00096144 1.0665E-04 4.5948E-05 Leptospira borgpetersenii Pathogany (infecting mice) Bacteria Legionellales 0.002333333 0.014135181 6.2940E-05 3.1533E-05 Mycoplasma penetrans Pathogany (infecting mice) Mycoplasma 0.0018 0.014209115 2.4312E-05 1.5115E-05 Paracoccidioides brasiliensis Pathogany (infecting mice) Fungi 0.001 0.000499713 7.2846E-05 4.3384E-05 Rhodobacter capsulatus Unreported Bacteria Rhodobacterales 0.001333333 0.001634871 1.2132E-04 4.4714E-05 Acetobacter tropicalis Unreported Bacteria 0.001333333 0.002692973 2.9932E-05 1.5084E-05 Cellulophaga phage phi19:1 Unreported Virus 0.003333333 0.008122172 5.1419E-06 7.1203E-07 Tessaracoccus aquimaris Unreported Bacteria Propionibacteriales 0.002933333 0.000772982 1.5977E-04 8.0103E-05 Thermocrinis albus Unreported Bacteria Aquificales 0.002333333 0.001225119 3.2967E-05 7.3177E-06 halophilic archaeon DL31 Unreported Archaea 0.002333333 0.004364837 2.8682E-05 1.4195E-05 Streptomyces sp. GBA 94-10 Unreported Bacteria Streptomycetales 0.002 0.015059096 5.8274E-05 2.4043E-05 Chthonomonas calidirosea Unreported Bacteria Chthonomonadales 0.002 0.003175406 6.6221E-05 2.0497E-05 Lutibacter profundi Unreported Bacteria 0.002 0.012388797 6.9978E-05 4.4559E-05 complex sp. 35734 Unreported Bacteria Enterobacterales 0.002 0.025039797 5.0645E-05 8.4808E-06 Bathymodiolus septemdierum thioautotrophic gill symbiont Unreported Bacteria 0.002 8.12284E-05 1.9922E-05 1.1641E-05 Hammondia hammondi Unreported Parasite 0.002 0.01219127 1.8657E-04 1.1765E-04 Edwardsiella phage PEi20 Unreported Virus 0.002 0.005972022 1.3045E-05 7.4631E-07 Microbulbifer agarilyticus Unreported Bacteria Cellvibrionales 0.0016 6.71021E-05 3.6501E-05 2.2731E-05 Parvibaculum lavamentivorans Unreported Bacteria Rhizobiales 0.0016 0.005553949 1.0266E-04 6.3333E-05 Thielavia terrestris Unreported Fungi 0.001466667 0.03131429 1.2684E-04 8.9564E-05 Veillonella rodentium Unreported Bacteria Veillonellales 0.001333333 0.026301936 1.1501E-04 7.6491E-05 Mycobacterium sp. WY10 Unreported Bacteria Corynebacteriales 0.001333333 0.001679688 1.0795E-05 5.6407E-06 choanae Unreported Bacteria Propionibacteriales 0.001333333 0.001752489 4.6754E-05 2.8824E-05 Tenericutes bacterium MO-XQ Unreported Bacteria unclassified Tenericutes 0.001333333 0.010895761 8.5206E-05 5.8651E-05 Pseudomonas savastanoi Unreported Bacteria Pseudomonadales 0.001333333 0.000487371 1.2039E-05 3.7777E-06 Pseudomonas psychrotolerans Unreported Bacteria Pseudomonadales 0.001333333 0.010464629 3.3400E-05 2.0807E-05 Pseudomonas psychrophila Unreported Bacteria Pseudomonadales 0.001333333 0.00759328 2.4340E-05 1.1078E-05 Pseudomonas sp. PONIH3 Unreported Bacteria Pseudomonadales 0.001333333 0.004419775 4.5263E-05 1.4885E-05 sp. PRwf-1 Unreported Bacteria Pseudomonadales 0.001333333 0.009784621 4.1590E-05 6.8389E-06 Stenotrophomonas sp. WZN-1 Unreported Bacteria 0.001333333 0.016570077 1.0117E-04 4.0934E-05 Alteromonas sp. RW2A1 Unreported Bacteria Alteromonadales 0.001333333 2.0299E-05 2.3511E-05 6.3903E-06 Sinorhizobium sp. CCBAU 05631 Unreported Bacteria Rhizobiales 0.001333333 0.003366292 1.2685E-05 5.0010E-06 Ensifer sojae Unreported Bacteria Rhizobiales 0.001333333 0.000235271 5.5267E-05 3.1256E-05 Bradyrhizobium sp. WSM471 Unreported Bacteria Rhizobiales 0.001333333 0.007090958 1.8885E-05 1.1666E-05 Rhodomicrobium vannielii Unreported Bacteria Rhizobiales 0.001333333 0.000845025 5.5689E-05 2.8716E-05 canadensis Unreported Bacteria 0.001333333 0.010681269 1.0533E-05 3.4078E-06 Nitrosomonas communis Unreported Bacteria Nitrosomonadales 0.001333333 0.000127601 3.2601E-05 1.5366E-05 Methanobrevibacter millerae Unreported Archaea 0.001333333 0.008346112 4.9261E-05 2.0660E-05 Lactobacillus prophage Lj771 Unreported Virus 0.001333333 0.002946531 2.5356E-06 6.1759E-08 Beihai tombus-like virus 19 Unreported Virus 0.001333333 0.001201982 4.8762E-07 5.7830E-08 Bacillus sp. FJAT-22090 Unreported Bacteria Bacillales 0.001 0.027450499 1.1774E-04 4.9264E-05 Streptomyces sp. P3 Unreported Bacteria Streptomycetales 0.001 0.006365747 7.9812E-05 3.6799E-05 Mycobacteroides saopaulense Unreported Bacteria Corynebacteriales 0.001 0.044473572 2.9008E-05 1.7792E-05 Arthrobacter sp. Rue61a Unreported Bacteria Micrococcales 0.001 0.003741133 2.9955E-05 9.4745E-06 Synechococcus sp. SynAce01 Unreported Bacteria Synechococcales 0.001 0.015984543 6.7792E-05 2.9752E-05 Mesoplasma coleopterae Unreported Bacteria Entomoplasmatales 0.001 0.009546766 7.6010E-06 1.6952E-06 Deinococcus maricopensis Unreported Bacteria Deinococcales 0.001 0.001004967 6.9074E-05 4.4474E-05 Pseudomonas libanensis Unreported Bacteria Pseudomonadales 0.001 0.005894928 1.1332E-05 4.6939E-06 Pseudomonas sabulinigri Unreported Bacteria Pseudomonadales 0.001 0.000393242 5.7174E-05 2.1320E-05 Shewanella oneidensis Unreported Bacteria Alteromonadales 0.001 0.033150196 3.4702E-05 1.4294E-05 Pseudoalteromonas nigrifaciens Unreported Bacteria Alteromonadales 0.001 0.000379106 1.6311E-05 5.6732E-06 Candidatus Evansia muelleri Unreported Bacteria Oceanospirillales 0.001 0.034612534 1.5030E-05 1.0039E-05 Bradyrhizobium ottawaense Unreported Bacteria Rhizobiales 0.001 0.017567641 8.6642E-05 5.3294E-05 Methylobacterium sp. 17Sr1-28 Unreported Bacteria Rhizobiales 0.001 0.035848491 4.4367E-05 3.8793E-05 Sphingomonas indica Unreported Bacteria 0.001 0.000549312 7.3504E-05 3.9482E-05 Candidatus Pelagibacter sp. IMCC9063 Unreported Bacteria 0.001 0.004091874 2.6972E-05 1.0400E-05 Candidatus Pelagibacter sp. RS40 Unreported Bacteria Pelagibacterales 0.001 0.042867375 5.3751E-05 2.0882E-05 xenovorans Unreported Bacteria Burkholderiales 0.001 0.000463952 1.3841E-04 7.6881E-05 Limnohabitans sp. 103DPR2 Unreported Bacteria Burkholderiales 0.001 0.001232489 2.3052E-05 1.2831E-05 Desulfococcus oleovorans Unreported Bacteria Desulfobacterales 0.001 0.00690807 2.0811E-04 1.0648E-04 Clavispora lusitaniae Unreported Fungi 0.001 0.007171774 3.6738E-05 2.1731E-05 Methanocaldococcus vulcanius Unreported Archaea 0.001 0.007019324 2.3970E-05 1.1271E-05 Methanocaldococcus jannaschii Unreported Archaea 0.001 0.000519806 4.3441E-05 1.6252E-05 Halostagnicola larsenii Unreported Archaea 0.001 0.015584216 2.5602E-05 1.2697E-05 Thermococcus guaymasensis Unreported Archaea 0.001 0.022884327 2.9386E-06 1.4182E-06 Pseudoalteromonas phage Pq0 Unreported Virus 0.001 0.00999331 3.5955E-06 3.6575E-07 Streptomyces virus phiHau3 Unreported Virus 0.001 0.011756546 2.0461E-07 0.0000E+00 Gramella sp. MAR_2010_102 Unreported Bacteria Flavobacteriales 0.003 0.001791688 4.1825E-05 7.9244E-05 Chryseobacterium camelliae Unreported Bacteria Flavobacteriales 0.0026 0.009001741 2.5852E-04 3.8256E-04 Fusarium fujikuroi Unreported Fungi 0.002 0.000990157 8.0792E-05 1.0922E-04 Alcanivorax xenomutans Unreported Bacteria Oceanospirillales 0.0016 0.00773828 1.8349E-04 3.0597E-04 Cohaesibacter sp. ES.047 Unreported Bacteria Rhizobiales 0.0016 0.011800945 6.5652E-05 1.0875E-04 linens Unreported Bacteria Micrococcales 0.001333333 0.006465691 8.9735E-05 1.5024E-04 Luteipulveratus mongoliensis Unreported Bacteria Micrococcales 0.001333333 0.0139977 4.7012E-05 8.1094E-05 Bacteroides caecimuris Unreported Bacteria Bacteroidales 0.001333333 0.00117423 3.1016E-02 6.5408E-02 Capnocytophaga leadbetteri Unreported Bacteria Flavobacteriales 0.001333333 0.006245926 2.1355E-04 3.3507E-04 Nonlabens dokdonensis Unreported Bacteria Flavobacteriales 0.001333333 0.002320414 4.0503E-05 5.8188E-05 Pedobacter ginsengisoli Unreported Bacteria Sphingobacteriales 0.001333333 0.010718092 1.1110E-04 1.5149E-04 Pectobacterium carotovorum Unreported Bacteria Enterobacterales 0.001333333 0.021103602 1.8226E-04 2.5508E-04 Rhizobium sp. IE4771 Unreported Bacteria Rhizobiales 0.001333333 0.00115836 2.8117E-05 6.7220E-05 Mesorhizobium sp. WSM1497 Unreported Bacteria Rhizobiales 0.001333333 0.003071993 1.4830E-05 3.2945E-05 Beijerinckia indica Unreported Bacteria Rhizobiales 0.001333333 0.000121413 2.7633E-05 5.0881E-05 Paraburkholderia terrae Unreported Bacteria Burkholderiales 0.001333333 0.005533727 8.0869E-04 1.5946E-03 gaditana Unreported Parasite 0.001333333 0.007926214 8.7662E-05 1.2703E-04 Tannerella forsythia Unreported Bacteria Bacteroidales 0.001 0.009577422 1.5337E-03 2.7449E-03 Aequorivita sublithincola Unreported Bacteria Flavobacteriales 0.001 0.007878848 6.5853E-05 1.0040E-04 Filimonas lacunae Unreported Bacteria Chitinophagales 0.001 0.02523027 1.4025E-04 1.7574E-04 Pseudomonas veronii Unreported Bacteria Pseudomonadales 0.001 0.000520517 1.3912E-05 4.2291E-05 Marinomonas mediterranea Unreported Bacteria Oceanospirillales 0.001 0.006923504 4.8654E-05 8.4432E-05 Aeromonas sp. ASNIH5 Unreported Bacteria 0.001 0.007973133 2.2313E-04 6.6562E-04 Kuraishia capsulata Unreported Fungi 0.001 0.000413482 3.0543E-05 5.3471E-05 Bacillus phage Stitch Unreported Virus 0.001 0.00404971 4.0479E-06 1.1735E-05

Table S8. Species identified by random forests analysis of shotgun sequencing data that exhibit significant differences in their representation in the fecal microbiomes between each two groups of mice. (b) Species discriminating fecal microbiota of the SS and Control mice. Mean importance of species identified by random forest are shown in the 5th column. Random forests assigns an importance score to each species by estimating the increase in error caused by removing that species from the set of predictors. In our analysis, we considered a species to be “highly predictive” if its importance score was at least 0.001. T-test was performed for the relative abundances of each species between the two groups of mice. P-values were at least 0.05 to be considered statistically significant.

Microbiological Taxonomy Random Forests Mean of relative abundance P-Value Species Microbiological Function (T-Test) Classification Bacterial Order Importance Score SS Control Streptomyces ambofaciens Engineered strain Bacteria Streptomycetales 0.002 0.000268949 5.4252E-05 3.9128E-05 Streptomyces lavendulae Engineered strain Bacteria Streptomycetales 0.001 4.9561E-05 7.6395E-05 4.3254E-05 Trichoderma reesei Engineered strain Fungi 0.001 0.000667934 8.1499E-05 5.1808E-05 Halomonas campaniensis Engineered strain Bacteria Oceanospirillales 0.001 0.043989708 3.0303E-05 4.5229E-05 Escherichia virus HK578 Antibiotic Virus 0.003 0.015661883 7.8987E-07 0.0000E+00 Stereum hirsutum Antibiotic Fungi 0.002 0.000295994 8.2713E-05 5.8432E-05 Trichoderma virens Antibiotic Fungi 0.001333333 0.002130615 7.1036E-05 4.4797E-05 Phialocephala scopiformis Antibiotic Fungi 0.001333333 0.00086365 8.0881E-05 5.3837E-05 Rhizophagus irregularis Antibiotic Fungi 0.001333333 0.004516615 4.9396E-04 3.2387E-04 Bacillus atrophaeus Antibiotic Bacteria Streptomycetales 0.001 0.006677889 4.8406E-05 2.8598E-05 Streptomyces albus Antibiotic Bacteria Bacillales 0.001 0.00868969 1.7165E-04 1.3786E-04 Pseudoalteromonas piscicida Antibiotic Bacteria Alteromonadales 0.001333333 0.02699621 5.9097E-05 8.2059E-05 Rhinocladiella mackenziei Pathogany (no infecting mice) Fungi 0.0026 0.00182535 3.9778E-05 2.3418E-05 Borreliella burgdorferi Pathogany (no infecting mice) Bacteria Spirochaetales 0.002333333 0.003340941 3.6825E-05 1.7778E-05 Theileria parva Pathogany (no infecting mice) Parasite 0.002333333 0.000530681 3.1056E-05 1.3828E-05 Parachlamydia acanthamoebae Pathogany (no infecting mice) Bacteria Parachlamydiales 0.002133333 0.006424318 2.3418E-05 1.5029E-05 Pathogany (no infecting mice) Bacteria Rickettsiales 0.002 0.000322054 3.0532E-05 1.4432E-05 Bordetella avium Pathogany (no infecting mice) Bacteria Burkholderiales 0.002 0.000308937 5.7819E-05 3.0745E-05 Campylobacter helveticus Pathogany (no infecting mice) Bacteria 0.002 0.000326507 7.2483E-05 3.6854E-05 Erysipelothrix rhusiopathiae Pathogany (no infecting mice) Bacteria Erysipelotrichales 0.001333333 0.001413285 9.7523E-05 5.8717E-05 Mycoplasma hyopneumoniae Pathogany (no infecting mice) Bacteria Mycoplasmataceae 0.001333333 0.002723375 3.2056E-05 1.6326E-05 Aspergillus fumigatus Pathogany (no infecting mice) Fungi 0.001333333 0.000716379 9.4038E-05 5.7807E-05 Plasmodium cynomolgi Pathogany (no infecting mice) Parasite 0.001333333 0.001250626 5.6011E-05 3.6275E-05 Spodoptera frugiperda granulovirus Pathogany (no infecting mice) Virus 0.001333333 0.035422595 2.4006E-06 1.1975E-06 Brucella sp. 09RB8471 Pathogany (no infecting mice) Bacteria Rhizobiales 0.001 0.004220841 4.1268E-06 1.4333E-06 Campylobacter hominis Pathogany (no infecting mice) Bacteria Campylobacterales 0.001 0.003213484 5.6551E-05 3.3226E-05 Chlamydia psittaci Pathogany (no infecting mice) Bacteria Chlamydiales 0.001 0.016941164 1.2278E-05 5.9137E-06 Fusobacterium varium Pathogany (no infecting mice) Bacteria Fusobacteriales 0.001 0.021336626 2.3075E-04 1.3074E-04 Talaromyces marneffei Pathogany (no infecting mice) Fungi 0.001 0.002821336 1.7376E-04 1.1715E-04 Porphyromonas asaccharolytica Pathogany (no infecting mice) Bacteria Bacteroidales 0.001 0.024487043 8.9152E-04 1.3307E-03 Toxoplasma gondii Pathogany (infecting mice) Parasite 0.001 0.003292539 2.7327E-04 1.7847E-04 Taterapox virus Pathogany (infecting mice) Virus 0.001333333 0.02358055 1.0777E-06 2.0822E-07 Rhodobacter capsulatus Unreported Bacteria Rhodobacterales 0.001333333 0.005730091 7.8099E-05 4.4714E-05 Meira miltonrushii Unreported Fungi 0.001 0.010742605 2.8681E-05 2.0953E-05 Dolichospermum compactum Unreported Bacteria Nostocales 0.003333333 0.017574855 3.5750E-05 2.0337E-05 Calothrix sp. NIES-2100 Unreported Bacteria Nostocales 0.002 0.000952862 5.1765E-05 2.6830E-05 Onion yellows phytoplasma Unreported Bacteria Acholeplasmatales 0.002 0.000885053 2.3507E-05 1.3747E-05 Pseudomonas lini Unreported Bacteria Pseudomonadales 0.002 0.00081848 1.5627E-05 7.8351E-06 Thiolapillus brandeum Unreported Bacteria Gammaproteobacteria 0.002 0.002873574 6.0758E-05 4.1756E-05 Agrobacterium sp. RAC06 Unreported Bacteria Rhizobiales 0.002 0.003069667 3.8184E-05 2.7451E-05 Aureobasidium namibiae Unreported Fungi 0.002 0.000995405 5.2067E-05 3.7943E-05 Spodoptera exigua iflavirus 2 Unreported Virus 0.002 0.016142365 3.0212E-07 0.0000E+00 Olsenella sp. oral taxon 807 Unreported Bacteria Coriobacteriales 0.0016 0.003863894 1.4591E-04 1.0620E-04 Rhizobium sp. NT-26 Unreported Bacteria Rhizobiales 0.0016 0.000110988 4.3488E-05 2.9960E-05 Exiguobacterium oxidotolerans Unreported Bacteria Bacillales 0.001333333 0.01152254 2.0255E-03 1.1141E-03 Rhodococcus jostii Unreported Bacteria Corynebacteriales 0.001333333 0.000280949 2.9280E-05 1.8421E-05 Blastococcus saxobsidens Unreported Bacteria Geodermatophilales 0.001333333 0.003214164 6.3828E-05 4.0154E-05 Acidimicrobium ferrooxidans Unreported Bacteria Acidimicrobiales 0.001333333 1.26807E-05 3.8829E-05 2.7889E-05 Nostoc sp. PCC 7107 Unreported Bacteria Nostocales 0.001333333 0.007107775 2.0359E-05 7.9677E-06 Spiroplasma cantharicola Unreported Bacteria Entomoplasmatales 0.001333333 0.011883519 3.1890E-05 1.5726E-05 Tenacibaculum jejuense Unreported Bacteria Flavobacteriales 0.001333333 0.003312625 7.2887E-05 4.7970E-05 Winogradskyella sp. J14-2 Unreported Bacteria Flavobacteriales 0.001333333 0.002956365 4.0613E-05 2.0886E-05 Pseudomonas taetrolens Unreported Bacteria Pseudomonadales 0.001333333 0.002955254 2.6893E-05 1.5201E-05 Croceicoccus marinus Unreported Bacteria Sphingomonadales 0.001333333 0.001019585 3.9205E-05 2.3268E-05 Defluviimonas alba Unreported Bacteria Rhodobacterales 0.001333333 0.047844702 6.7539E-05 5.0714E-05 Limnohabitans sp. 103DPR2 Unreported Bacteria Burkholderiales 0.001333333 0.003311425 2.5321E-05 1.2831E-05 Vitreoscilla sp. C1 Unreported Bacteria Neisseriales 0.001333333 0.045534115 2.0241E-05 1.2985E-05 Thermocrinis ruber Unreported Bacteria Aquificales 0.001333333 0.018850164 1.1977E-05 6.4216E-06 Aciduliprofundum boonei Unreported Archaea 0.001333333 0.004475027 1.3854E-05 5.8615E-06 Lactobacillus phage KC5a Unreported Virus 0.001333333 0.015657553 6.4965E-05 2.7743E-06 Staphylococcus virus S253 Unreported Virus 0.001333333 0.042179608 9.5830E-07 0.0000E+00 Kern Canyon ledantevirus Unreported Virus 0.001333333 0.007182333 3.1895E-04 1.5081E-04 Thermoanaerobacterium thermosaccharolyticum Unreported Bacteria Thermoanaerobacterales 0.001 0.01648749 2.3012E-04 1.5207E-04 Thermoanaerobacterium xylanolyticum Unreported Bacteria Thermoanaerobacterales 0.001 0.011449986 7.7359E-05 4.1769E-05 Bacillus kochii Unreported Bacteria Bacillales 0.001 0.007147814 7.7157E-05 4.6607E-05 Nocardia terpenica Unreported Bacteria Corynebacteriales 0.001 0.003521374 5.9248E-05 4.7702E-05 Aurantimicrobium minutum Unreported Bacteria Micrococcales 0.001 0.007914226 8.5012E-06 4.0783E-06 Friedmanniella luteola Unreported Bacteria Propionibacteriales 0.001 0.00400437 4.9997E-05 3.4316E-05 Micromonospora sp. WMMA2032 Unreported Bacteria Micromonosporales 0.001 0.016206915 4.3392E-05 2.9454E-05 Bacteroides cellulosilyticus Unreported Bacteria Bacteroidales 0.001 0.01899505 1.1027E-02 4.8263E-03 Dickeya sp. NCPPB 3274 Unreported Bacteria Enterobacterales 0.001 0.013566669 2.1557E-05 1.1949E-05 Psychrobacter arcticus Unreported Bacteria Pseudomonadales 0.001 0.01625408 1.4648E-05 9.7411E-06 Marinobacter hydrocarbonoclasticus Unreported Bacteria Alteromonadales 0.001 0.033274632 4.9440E-05 3.4272E-05 Colwellia sp. MT41 Unreported Bacteria Alteromonadales 0.001 0.034875788 2.0706E-05 1.4152E-05 Reinekea forsetii Unreported Bacteria Oceanospirillales 0.001 0.002254192 4.0682E-05 2.7295E-05 Teredinibacter turnerae Unreported Bacteria Cellvibrionales 0.001 0.004923788 3.7012E-05 2.3009E-05 Azospirillum lipoferum Unreported Unreported 0.001 0.00254135 1.3590E-04 9.7832E-05 Burkholderia glumae Unreported Bacteria Burkholderiales 0.001 7.99878E-05 5.7486E-05 3.5102E-05 Pandoraea norimbergensis Unreported Bacteria Burkholderiales 0.001 0.001489094 3.6530E-05 2.2176E-05 Arcobacter sp. LPB0137 Unreported Bacteria Campylobacterales 0.001 0.013788568 7.2845E-05 3.9748E-05 Methanomethylovorans hollandica Unreported Archaea 0.001 0.001247248 3.0926E-05 1.9942E-05 Thermococcus cleftensis Unreported Archaea 0.001 0.001495193 1.7320E-05 9.3672E-06 Metallosphaera hakonensis Unreported Archaea 0.001 0.024793421 3.4561E-06 1.4732E-06 Vulcanisaeta moutnovskia Unreported Archaea 0.001 0.027771193 4.6098E-06 2.1096E-06 Loktanella phage pCB2051-A Unreported Virus 0.001 0.0409972 8.6114E-08 0.0000E+00 Melon severe mosaic tospovirus Unreported Virus 0.001 0.000993693 2.1034E-06 7.8572E-07 begomovirus satellite DNA beta Unreported Virus 0.001 0.028765992 2.1059E-07 2.5314E-08 Cyanothece sp. PCC 7424 Unreported Bacteria Chroococcales 0.001 0.032173523 3.7059E-05 2.3173E-05 Pseudomonas lurida Unreported Bacteria Pseudomonadales 0.004 0.001441666 1.0098E-05 4.0320E-05 Rothia dentocariosa Unreported Bacteria Micrococcales 0.002333333 0.009672091 3.4289E-05 4.6308E-05 Nocardia soli Unreported Bacteria Corynebacteriales 0.002 0.001033982 4.5489E-05 6.6670E-05 Croceibacter atlanticus Unreported Bacteria Flavobacteriales 0.002 0.008946508 7.7764E-05 1.2575E-04 Fibrella sp. ES10-3-2-2 Unreported Bacteria Cytophagales 0.002 0.011868416 2.3953E-04 3.8825E-04 Marinobacter similis Unreported Bacteria Alteromonadales 0.002 0.001407531 2.5636E-05 3.1944E-05 Saccharomonospora azurea Unreported Bacteria Pseudonocardiales 0.0016 0.000611547 6.8697E-05 1.1335E-04 Chryseobacterium taklimakanense Unreported Bacteria Flavobacteriales 0.001333333 0.029341585 3.1229E-04 4.3287E-04 Mucilaginibacter sp. BJC16-A31 Unreported Bacteria Sphingobacteriales 0.001333333 0.011542665 1.2496E-04 1.5356E-04 Chlorobium limicola Unreported Bacteria Chlorobiales 0.001333333 0.010054097 1.0596E-04 1.4075E-04 Aeromonas sp. ASNIH5 Unreported Bacteria Aeromonadales 0.001333333 0.022036007 3.1229E-04 6.6562E-04 Nitratifractor salsuginis Unreported Bacteria Campylobacterales 0.001333333 0.00466546 1.3036E-04 2.4037E-04 Bacteriovorax stolpii Unreported Bacteria Bacteriovoracales 0.001333333 0.008902466 4.6616E-05 6.8104E-05 Escherichia virus K1G Unreported Virus 0.001333333 0.023417256 0.0000E+00 4.5368E-07 Planococcus kocurii Unreported Bacteria Bacillales 0.001 0.003922371 3.0370E-05 4.5427E-05 Microbacterium sp. TPU 3598 Unreported Bacteria Micrococcales 0.001 0.005108234 4.7490E-05 6.3532E-05 bacterium IMCC26103 Unreported Bacteria unclassified Actinobacteria 0.001 0.01501745 2.6879E-05 4.5595E-05 Cycloclasticus zancles Unreported Bacteria 0.001 0.00196195 3.1290E-05 6.3742E-05 Blastomonas sp. RAC04 Unreported Bacteria Sphingomonadales 0.001 0.026103196 6.5875E-05 9.1365E-05 Paraburkholderia hospita Unreported Bacteria Burkholderiales 0.001 0.036987158 3.4089E-05 4.5204E-05

Table S8. Species identified by random forests analysis of shotgun sequencing data that exhibit significant differences in their representation in the fecal microbiomes between each two groups of mice. (c) Species discriminating fecal microbiota of the MW and Control mice. Mean importance of species identified by random forest are shown in the 5th column. Random forests assigns an importance score to each species by estimating the increase in error caused by removing that species from the set of predictors. In our analysis, we considered a species to be “highly predictive” if its importance score was at least 0.001. T-test was performed for the relative abundances of each species between the two groups of mice. P-values were at least 0.05 to be considered statistically significant.

Microbiological Taxonomy Random Forests P-Value Mean of relative abundance Species Microbiological Function (T-Test) Classification Bacterial Order Importance Score MW Control sp. JS614 Engineered strain Bacteria Propionibacteriales 0.003 0.011430126 5.7503E-05 3.0117E-05 Meiothermus ruber Engineered strain Bacteria Thermales 0.003 0.030228878 6.5143E-05 3.8273E-05 Bacillus megaterium Engineered strain Bacteria Bacillales 0.002666667 0.009394466 1.8614E-04 1.2455E-04 Clostridium aceticum Engineered strain Bacteria Clostridiales 0.002333333 0.00858805 1.5341E-04 9.5251E-05 Clostridium tyrobutyricum Engineered strain Bacteria Clostridiales 0.001333333 0.033700787 1.5766E-04 1.1050E-04 Caldicellulosiruptor owensensis Engineered strain Bacteria Thermoanaerobacterales 0.001333333 0.000614232 5.7073E-05 3.2594E-05 Rubrobacter xylanophilus Engineered strain Bacteria Rubrobacterales 0.001333333 0.043896967 7.8411E-05 5.1540E-05 Nostoc piscinale Engineered strain Bacteria Nostocales 0.001333333 0.025602589 2.4362E-05 1.5919E-05 Stereum hirsutum Antibiotic Fungi 0.002333333 0.000461012 7.6594E-05 5.8432E-05 Streptomyces sp. Mg1 Antibiotic Bacteria Streptomycetales 0.002 0.008247334 6.8260E-05 5.0762E-05 Faecalibacterium prausnitzii Antibiotic Bacteria Clostridiales 0.001333333 0.037496545 5.8946E-03 3.6760E-03 Actinosynnema pretiosum Antibiotic Bacteria Pseudonocardiales 0.001 0.026305663 6.7499E-05 4.7803E-05 Bacteroides ovatus Antibiotic Bacteria Bacteroidales 0.001333333 0.012403301 4.0877E-03 7.2320E-03 Vibrio tapetis Pathogany (no infecting mice) Bacteria Vibrionales 0.001333333 0.00481333 2.5505E-05 1.5880E-05 Torque teno midi virus 2 Pathogany (no infecting mice) Virus 0.001333333 0.032401126 2.1041E-07 2.5314E-08 Mogibacterium pumilum Pathogany (no infecting mice) Bacteria Clostridiales 0.001 0.019186338 1.7195E-04 1.1841E-04 Bacillus anthracis Pathogany (no infecting mice) Bacteria Bacillales 0.001 0.033566203 3.3272E-04 1.4402E-04 Photorhabdus asymbiotica Pathogany (no infecting mice) Bacteria Enterobacterales 0.001 0.016439303 5.9113E-05 4.4808E-05 Rhodobacter capsulatus Unreported Bacteria Rhodobacterales 0.001 0.008608414 6.5874E-05 4.4714E-05 Mesoplasma chauliocola Unreported Bacteria Entomoplasmatales 0.003333333 0.037423292 4.5611E-05 2.8741E-05 Paenibacillus terrae Unreported Bacteria Bacillales 0.003 0.006393729 8.4452E-05 5.5489E-05 Planktomarina temperata Unreported Bacteria Rhodobacterales 0.002666667 0.014633701 2.7755E-05 1.3861E-05 Ruminiclostridium thermocellum Unreported Bacteria Clostridiales 0.002333333 0.020050581 2.7820E-04 1.7465E-04 Acaromyces ingoldii Unreported Fungi 0.002 0.000197209 6.4340E-05 4.5047E-05 Pseudomonas lini Unreported Bacteria Pseudomonadales 0.0016 0.001196111 1.4785E-05 7.8351E-06 Staphylococcus sp. AntiMn-1 Unreported Bacteria Bacillales 0.001333333 0.003155694 2.0169E-05 6.6269E-06 Streptomyces rubrolavendulae Unreported Bacteria Streptomycetales 0.001333333 0.013514947 4.3421E-05 2.5961E-05 Nocardia terpenica Unreported Bacteria Corynebacteriales 0.001333333 0.007555551 6.2820E-05 4.7702E-05 Candidatus Moranella endobia Unreported Bacteria Enterobacterales 0.001333333 0.033603798 8.2597E-06 3.7082E-06 Pantoea vagans Unreported Bacteria Enterobacterales 0.001333333 0.025049816 1.3626E-04 8.2616E-05 Xanthomonas fragariae Unreported Bacteria Xanthomonadales 0.001333333 0.012851595 1.8636E-05 1.1969E-05 Symbiobacterium thermophilum Unreported Bacteria Clostridiales 0.001 0.028194496 2.2909E-04 1.4898E-04 Syntrophomonas wolfei Unreported Bacteria Clostridiales 0.001 0.005947935 9.1698E-05 6.8516E-05 Bacillus sp. 1NLA3E Unreported Bacteria Bacillales 0.001 0.008663487 1.0548E-04 6.4696E-05 Bacillus gobiensis Unreported Bacteria Bacillales 0.001 0.006562851 6.6023E-05 3.9686E-05 Streptococcus himalayensis Unreported Bacteria Bacillales 0.001 0.005746087 3.1635E-05 1.9575E-05 Streptomyces sp. CCM_MD2014 Unreported Bacteria Bacillales 0.001 0.028791616 4.0320E-05 2.3655E-05 Micromonospora echinaurantiaca Unreported Bacteria Micromonosporales 0.001 0.00445964 6.2871E-05 4.4147E-05 Bifidobacterium kashiwanohense Unreported Bacteria Bifidobacteriales 0.001 0.003663959 1.4265E-04 9.8769E-05 Nostoc sp. PCC 7120 Unreported Bacteria Nostocales 0.001 0.027628006 4.9753E-05 3.4318E-05 Deinococcus puniceus Unreported Bacteria Deinococcales 0.001 0.009659706 4.4189E-05 3.0903E-05 Agarivorans gilvus Unreported Bacteria Alteromonadales 0.001 0.002330887 3.4809E-05 2.3294E-05 Burkholderia sp. MSMB0856 Unreported Bacteria Burkholderiales 0.001 0.008750984 1.4724E-05 7.9952E-06 Acidovorax sp. T1 Unreported Bacteria Burkholderiales 0.001 0.032369551 2.3044E-04 1.9155E-04 Halorubrum lacusprofundi Unreported Archaea 0.001 0.002352489 1.5648E-05 7.9938E-06 Pseudomonas phage phiPsa374 Unreported Virus 0.001 0.04098891 2.7658E-07 5.3480E-08 Erwinia phage vB_EamM_ChrisDB Unreported Virus 0.001 0.042103612 7.6326E-07 3.1260E-08 Pseudomonas virus PaMx74 Unreported Virus 0.001 0.022724084 1.0644E-06 4.6658E-07 Methylocystis sp. SC2 Unreported Bacteria Rhizobiales 0.0018 0.002954292 3.0382E-05 4.5321E-05 Acinetobacter sp. ACNIH1 Unreported Bacteria Pseudomonadales 0.001333333 0.01109596 3.3874E-05 4.4427E-05 Thermococcus gammatolerans Unreported Archaea 0.001333333 0.003277469 9.2511E-06 1.3961E-05 Klebsiella quasivariicola Unreported Bacteria Enterobacterales 0.001 0.04606414 4.1991E-05 5.3543E-05

Table S8. Species identified by random forests analysis of shotgun sequencing data that exhibit significant differences in their representation in the fecal microbiomes between each two groups of mice. (d) Species discriminating fecal microbiota of the Soil and MW mice. Mean importance of species identified by random forest are shown in the 5th column. Random forests assigns an importance score to each species by estimating the increase in error caused by removing that species from the set of predictors. In our analysis, we considered a species to be “highly predictive” if its importance score was at least 0.001. T-test was performed for the relative abundances of each species between the two groups of mice. P-values were at least 0.05 to be considered statistically significant.

Microbiological Taxonomy Random Forests P-Value Mean of relative abundance Species Microbiological Function (T-Test) Classification Bacterial Order Importance Score Soil Control Rhodococcus rhodochrous Engineered strain Bacteria Corynebacteriales 0.001333333 1.18289E-05 3.3232E-05 1.5072E-05 Rubrivivax gelatinosus Engineered strain Bacteria Burkholderiales 0.001333333 0.012755716 1.2915E-04 7.9489E-05 Mycobacterium sp. VKM Ac-1817D Engineered strain Bacteria Corynebacteriales 0.001 0.045869094 1.1668E-04 4.9597E-05 Leptospirillum ferriphilum Engineered strain Bacteria Nitrospirales 0.002 0.028035501 1.7627E-05 3.3896E-05 Alteromonas naphthalenivorans Engineered strain Bacteria Alteromonadales 0.001333333 0.00864653 2.0747E-05 5.0976E-05 Vibrio gazogenes Antibiotic Bacteria Vibrionales 0.002 0.000209083 8.9855E-05 4.3803E-05 Lysobacter enzymogenes Antibiotic Bacteria Xanthomonadales 0.001333333 0.001111421 1.5780E-04 8.8710E-05 Penicillium rubens Antibiotic Fungi 0.001333333 0.017338223 1.1702E-04 1.9940E-04 Acinetobacter soli Pathogany (no infecting mice) Bacteria Pseudomonadales 0.002 0.004507329 2.59533E-05 1.2967E-05 Cupriavidus gilardii Pathogany (no infecting mice) Bacteria Burkholderiales 0.002 0.000831265 9.9992E-05 4.6739E-05 Ralstonia insidiosa Pathogany (no infecting mice) Bacteria Burkholderiales 0.001333333 0.000961507 1.0216E-04 5.7890E-05 Pathogany (no infecting mice) Bacteria Burkholderiales 0.001333333 0.000487417 6.7885E-05 3.9361E-05 simulans Pathogany (no infecting mice) Bacteria Corynebacteriales 0.001 0.001232652 1.0879E-04 6.0149E-05 Cronobacter sakazakii Pathogany (no infecting mice) Bacteria Enterobacterales 0.001 0.018646403 1.5166E-04 8.6109E-05 Pseudomonas cedrina Pathogany (no infecting mice) Bacteria Pseudomonadales 0.001 0.00037514 3.2397E-05 1.6150E-05 Trichophyton benhamiae Pathogany (no infecting mice) Fungi 0.001 0.001764652 6.9469E-05 3.3066E-05 Pathogany (no infecting mice) Bacteria Vibrionales 0.002 0.02218303 1.6227E-04 1.1913E-04 Staphylococcus haemolyticus Pathogany (no infecting mice) Bacteria Bacillales 0.002 0.016868638 9.1926E-05 1.7521E-04 Xestia c-nigrum granulovirus Pathogany (no infecting mice) Virus 0.0016 0.048496157 3.6002E-06 1.7688E-05 sp. HF Pathogany (no infecting mice) Bacteria Rickettsiales 0.001 0.013370884 6.3965E-06 1.6977E-05 Rhodobacter capsulatus Unreported Bacteria Rhodobacterales 0.001 0.009404073 1.2132E-04 6.5874E-05 Acetobacter tropicalis Unreported Bacteria Rhodospirillales 0.001 0.00752741 2.9932E-05 1.5608E-05 Francisella sp. TX077308 Unreported Bacteria Thiotrichales 0.004 0.00017081 3.4320E-05 1.7117E-05 Streptomyces violaceusniger Unreported Bacteria Streptomycetales 0.002 0.000165522 6.8344E-05 3.2323E-05 Mycolicibacterium thermoresistibile Unreported Bacteria Corynebacteriales 0.002 0.000543669 7.3501E-05 2.8580E-05 Rhodococcus ruber Unreported Bacteria Corynebacteriales 0.002 0.000145985 5.1289E-05 3.3116E-05 Amycolatopsis sp. BJA-103 Unreported Bacteria Pseudonocardiales 0.002 0.01175532 6.0356E-05 3.3900E-05 Psychrobacter sp. PRwf-1 Unreported Bacteria Pseudomonadales 0.002 0.0109612 4.1590E-05 7.4873E-06 Methylosinus trichosporium Unreported Bacteria Rhizobiales 0.002 0.031018836 4.5493E-05 3.6364E-05 Brevundimonas naejangsanensis Unreported Bacteria Caulobacterales 0.002 0.000405651 4.7554E-05 2.3376E-05 secondary of Heteropsylla cubana Unreported Bacteria Enterobacterales 0.0018 0.003089094 3.0538E-05 1.2741E-05 Burkholderia latens Unreported Bacteria Burkholderiales 0.0016 0.042831232 1.1661E-05 6.8654E-06 Bacillus sp. MD-5 Unreported Bacteria Bacillales 0.001333333 3.37884E-06 6.7261E-05 1.7849E-05 Corynebacterium uterequi Unreported Bacteria Corynebacteriales 0.001333333 0.009082506 5.2415E-05 2.9974E-05 Corynebacterium maris Unreported Bacteria Corynebacteriales 0.001333333 0.000137771 4.1778E-05 2.2975E-05 Candidatus Planktophila dulcis Unreported Bacteria Candidatus Nanopelagicales0.001333333 0.002157002 3.5966E-05 1.5623E-05 Psychrobacter sp. P2G3 Unreported Bacteria Pseudomonadales 0.001333333 0.010570921 2.6604E-05 7.7541E-06 Psychrobacter sp. YP14 Unreported Bacteria Pseudomonadales 0.001333333 0.000694302 3.6680E-05 8.5779E-06 Agrobacterium fabrum Unreported Bacteria Rhizobiales 0.001333333 0.025037233 4.1682E-05 3.3568E-05 Sphingomonas wittichii Unreported Bacteria Sphingomonadales 0.001333333 0.002351484 3.9800E-05 1.6459E-05 Burkholderia sp. NRF60-BP8 Unreported Bacteria Burkholderiales 0.001333333 0.00016691 2.2735E-05 7.8720E-06 Bordetella genomosp. 13 Unreported Bacteria Burkholderiales 0.001333333 0.000408116 1.6922E-04 9.3292E-05 Prochlorococcus phage P-TIM68 Unreported Virus 0.001333333 0.000438054 2.1566E-06 3.8354E-07 Cellulophaga phage phi19:1 Unreported Virus 0.001333333 0.013021903 5.1419E-06 9.7970E-07 Anatid alphaherpesvirus 1 Unreported Virus 0.001333333 0.018738881 4.3342E-07 0.0000E+00 Streptomyces formicae Unreported Bacteria Streptomycetales 0.001 0.002045923 1.0389E-04 6.9883E-05 Cellulosimicrobium cellulans Unreported Bacteria Micrococcales 0.001 0.002535106 4.3033E-05 2.5025E-05 Rhizobium sp. CIAT894 Unreported Bacteria Rhizobiales 0.001 0.000216201 4.0431E-05 1.9334E-05 Bradyrhizobium sp. ORS 278 Unreported Bacteria Rhizobiales 0.001 0.001331584 5.4113E-05 3.4094E-05 Sphingobium chlorophenolicum Unreported Bacteria Sphingomonadales 0.001 7.76426E-05 5.5242E-05 3.6491E-05 Burkholderia contaminans Unreported Bacteria Burkholderiales 0.001 0.005551675 6.0946E-05 2.1248E-05 Planctomyces sp. SH-PL14 Unreported Bacteria Planctomycetales 0.001 0.033758899 8.3875E-05 6.1970E-05 Thermotoga caldifontis Unreported Bacteria Thermotogales 0.001 0.034965259 3.6188E-05 2.5437E-05 Nitrospira japonica Unreported Bacteria Nitrospirales 0.001 0.044563742 7.0949E-05 3.9528E-05 Halobiforma lacisalsi Unreported Archaea 0.001 0.003321055 3.1990E-05 1.7524E-05 Thermogladius calderae Unreported Archaea 0.001 0.013932946 9.6095E-06 5.3873E-06 Lactobacillus phage phi jlb1 Unreported Virus 0.001 0.013402934 9.6716E-05 2.7285E-06 Lactobacillus prophage Lj771 Unreported Virus 0.001 0.008600863 2.5356E-06 3.8322E-07 Lactobacillus phage A2 Unreported Virus 0.001 0.044169888 4.5103E-05 1.4153E-05 Arthrobacter sp. ATCC 21022 Unreported Archaea 0.001333333 0.01210174 4.5225E-05 2.3678E-05 Pseudomonas palleroniana Unreported Bacteria Pseudomonadales 0.001333333 0.010237014 1.9886E-05 1.3260E-05 Rhodococcus sp. H-CA8f Unreported Bacteria Corynebacteriales 0.002 0.035191859 5.6354E-06 1.1104E-05 Oscillatoria nigro-viridis Unreported Bacteria Oscillatoriales 0.002 0.002521554 5.1116E-05 8.4229E-05 Enterobacter sp. R4-368 Unreported Bacteria Enterobacterales 0.002 0.00899265 3.7009E-05 6.2135E-05 Pseudomonas veronii Unreported Bacteria Pseudomonadales 0.002 0.004389812 1.3912E-05 3.8436E-05 Methanobrevibacter olleyae Unreported Archaea 0.002 0.00380547 8.5623E-05 1.2762E-04 Staphylococcus sp. AntiMn-1 Unreported Bacteria Bacillales 0.001333333 0.011618589 9.5609E-06 2.0169E-05 Arthrobacter sp. FB24 Unreported Bacteria Micrococcales 0.001333333 0.00472829 4.3988E-05 7.2191E-05 crassostreae Unreported Bacteria Flavobacteriales 0.001333333 0.001719044 3.9708E-05 6.3543E-05 Gramella sp. MAR_2010_102 Unreported Bacteria Flavobacteriales 0.001333333 0.004762576 4.1825E-05 7.6688E-05 Sphingorhabdus sp. YGSMI21 Unreported Bacteria Sphingomonadales 0.001333333 0.009924357 3.8601E-05 7.2964E-05 Penicillium arizonense Unreported Fungi 0.001333333 0.018898049 5.1932E-05 6.9965E-05 Capronia epimyces Unreported Fungi 0.001333333 0.026937472 8.2813E-05 2.1778E-04 Schizosaccharomyces japonicus Unreported Fungi 0.001333333 0.04626052 2.3338E-05 4.6032E-05 Wallemia ichthyophaga Unreported Fungi 0.001333333 0.000101894 2.0374E-05 3.9144E-05 Bacillus phage Stitch Unreported Virus 0.001333333 0.01612712 4.0479E-06 1.7088E-05 Brevibacterium linens Unreported Bacteria Micrococcales 0.001 0.024670568 8.9735E-05 1.3898E-04 Luteipulveratus mongoliensis Unreported Bacteria Micrococcales 0.001 0.034301189 4.7012E-05 6.5996E-05 Spiroplasma clarkii Unreported Bacteria Entomoplasmatales 0.001 0.037898071 1.8952E-05 3.4266E-05 Candidatus Phytoplasma mali Unreported Bacteria Acholeplasmatales 0.001 0.035305263 3.7747E-05 5.3301E-05 Winogradskyella sp. PC-19 Unreported Bacteria Flavobacteriales 0.001 0.003130119 4.0393E-05 6.2682E-05 Serratia sp. ATCC 39006 Unreported Bacteria Enterobacterales 0.001 0.000332847 5.8740E-05 1.1117E-04 sp. oral taxon 036 Unreported Bacteria Pasteurellales 0.001 0.028133098 4.3910E-06 8.0720E-06 Aspergillus glaucus Unreported Fungi 0.001 3.46038E-05 4.2318E-05 8.0719E-05 Mycobacterium virus Bxz1 Unreported Virus 0.001 0.037125218 1.9444E-06 2.9082E-06

Table S8. Species identified by random forests analysis of shotgun sequencing data that exhibit significant differences in their representation in the fecal microbiomes between each two groups of mice. (e) Species discriminating fecal microbiota of the SS and MW mice.Mean importance of species identified by random forest are shown in the 5th column. Random forests assigns an importance score to each species by estimating the increase in error caused by removing that species from the set of predictors. In our analysis, we considered a species to be “highly predictive” if its importance score was at least 0.001. T-test was performed for the relative abundances of each species between the two groups of mice. P-values were at least 0.05 to be considered statistically significant.

Microbiological Taxonomy Random Forests P-Value Mean of relative abundance Species Microbiological Function (T-Test) Classification Bacterial Order Importance Score SS MW Acinetobacter venetianus Engineered strain Bacteria Pseudomonadales 0.001 0.004252511 2.5491E-05 1.1399E-05 Variovorax paradoxus Engineered strain Bacteria Burkholderiales 0.001 0.004047201 1.9499E-04 1.3137E-04 Pseudomonas mediterranea Engineered strain Bacteria Pseudomonadales 0.001333333 0.040682765 2.4543E-05 1.7214E-05 Aspergillus bombycis Engineered strain Fungi 0.001333333 0.017882272 6.5778E-05 8.5164E-05 Bacillus sp. BH072 Antibiotic Bacteria Bacillales 0.001333333 0.006561487 3.3335E-05 0.0000E+00 Streptomyces sp. MOE7 Antibiotic Bacteria Streptomycetales 0.001333333 0.008206588 3.4607E-05 2.2142E-05 Chromobacterium violaceum Antibiotic Bacteria Neisseriales 0.001333333 0.005675009 1.0044E-04 8.3004E-05 Pathogany (no infecting mice) Bacteria Rickettsiales 0.002 0.02007675 2.0746E-06 3.6355E-08 Mycobacterium simiae Pathogany (no infecting mice) Bacteria Corynebacteriales 0.001333333 0.001899202 4.4489E-05 2.6563E-05 Desulfovibrio fairfieldensis Pathogany (no infecting mice) Bacteria Desulfovibrionales 0.001333333 0.003809476 7.2050E-04 1.5892E-03 Treponema paraluiscuniculi Pathogany (no infecting mice) Bacteria Spirochaetales 0.001333333 0.030162364 7.7201E-07 6.1465E-06 Vibrio tubiashii Pathogany (no infecting mice) Bacteria Vibrionales 0.001 0.005860801 2.1999E-05 3.2387E-05 Rhodococcus jostii Unreported Bacteria Corynebacteriales 0.005 0.002162462 2.9280E-05 1.9550E-05 Burkholderia metallica Unreported Bacteria Burkholderiales 0.002666667 0.003434121 2.1879E-05 1.5149E-05 Cardinium endosymbiont of Encarsia pergandiella Unreported Bacteria Cytophagales 0.002333333 0.028325117 1.4484E-05 1.0545E-05 Octadecabacter temperatus Unreported Bacteria Rhodobacterales 0.002 0.001156145 1.8943E-05 9.5674E-06 Burkholderia sp. NRF60-BP8 Unreported Bacteria Burkholderiales 0.002 0.002334702 1.4815E-05 7.8720E-06 Desulfurococcus amylolyticus Unreported Archaea 0.002 0.008772554 1.3551E-05 7.2366E-06 Nonlabens virus P12024S Unreported Virus 0.002 0.008697162 1.0460E-06 0.0000E+00 Clavibacter sepedonicus Unreported Bacteria Micrococcales 0.0016 0.003967448 3.3009E-05 2.0086E-05 variabilis Unreported Bacteria Micrococcales 0.0016 0.001562139 4.8265E-05 2.3867E-05 Burkholderia glumae Unreported Bacteria Burkholderiales 0.0016 0.001938973 5.7486E-05 4.1085E-05 Pantoea alhagi Unreported Bacteria Enterobacterales 0.001333333 0.029256332 7.7256E-05 6.3884E-05 Pseudomonas savastanoi Unreported Bacteria Pseudomonadales 0.001333333 0.009011593 1.2876E-05 5.3327E-06 Pseudomonas sihuiensis Unreported Bacteria Pseudomonadales 0.001333333 0.003330021 2.2881E-05 1.6033E-05 Psychrobacter sp. P2G3 Unreported Bacteria Pseudomonadales 0.001333333 0.005981157 1.3860E-05 7.7541E-06 Bradyrhizobium sp. ORS 278 Unreported Bacteria Rhizobiales 0.001333333 0.012828352 4.4935E-05 3.4094E-05 Sphingomonas sp. MM-1 Unreported Bacteria Sphingomonadales 0.001333333 0.003950789 1.2278E-04 9.0316E-05 Methylophilus sp. TWE2 Unreported Bacteria Nitrosomonadales 0.001333333 0.001797885 2.4527E-05 1.6519E-05 Polaribacter vadi Unreported Bacteria Flavobacteriales 0.001 0.001013947 5.6520E-05 4.1377E-05 aleksiciae Unreported Bacteria Enterobacterales 0.001 0.007639343 3.7616E-05 1.9030E-05 Xanthomonas albilineans Unreported Bacteria Xanthomonadales 0.001 0.016688499 2.2871E-05 1.6214E-05 Rhizobium sp. CIAT894 Unreported Bacteria Rhizobiales 0.001 0.00522234 3.2460E-05 1.9334E-05 Mesorhizobium sp. B7 Unreported Bacteria Rhizobiales 0.001 0.023244642 6.0996E-05 4.9277E-05 Ruegeria sp. TM1040 Unreported Bacteria Rhodobacterales 0.001 0.012425819 3.9332E-05 2.7378E-05 Burkholderia sp. MSMB1588 Unreported Bacteria Burkholderiales 0.001 0.024285728 2.3712E-05 1.1817E-05 Achromobacter sp. MFA1 R4 Unreported Bacteria Burkholderiales 0.001 0.030837941 4.7331E-05 3.4781E-05 Punctularia strigosozonata Unreported Fungi 0.001 0.001803795 7.1944E-05 4.1345E-05 Nitrososphaera viennensis Unreported Archaea 0.001 0.002213533 2.0193E-05 1.2808E-05 Pelagibacter phage HTVC008M Unreported Virus 0.001 0.002909922 6.9203E-07 1.3685E-07 Lactobacillus prophage Lj771 Unreported Virus 0.001 0.031808758 3.6533E-06 3.8322E-07 Melon severe mosaic tospovirus Unreported Virus 0.001 8.69888E-06 2.1034E-06 4.3535E-07 Tula orthohantavirus Unreported Virus 0.001333333 0.047215209 7.4854E-07 2.6138E-07 Dickeya dadantii Unreported Bacteria Enterobacterales 0.003666667 0.000890017 8.6528E-05 1.0539E-04 Methanosphaerula palustris Unreported Archaea 0.002333333 0.027744118 2.3710E-05 4.0452E-05 Amycolatopsis orientalis Unreported Bacteria Pseudonocardiales 0.002 0.013592453 6.5432E-05 8.5047E-05 Geobacillus thermocatenulatus Unreported Bacteria Bacillales 0.001333333 0.011372254 2.5284E-05 4.3054E-05 Planococcus kocurii Unreported Bacteria Bacillales 0.001333333 0.014325609 3.0370E-05 5.5237E-05 Streptomyces sampsonii Unreported Bacteria Streptomycetales 0.001333333 0.002118861 4.8583E-05 1.2944E-04 Mycolicibacter sinensis Unreported Bacteria Corynebacteriales 0.001333333 0.008197653 4.6721E-05 6.1706E-05 Pseudomonas lurida Unreported Bacteria Pseudomonadales 0.001333333 0.017629313 1.0098E-05 5.5324E-05 Shewanella putrefaciens Unreported Bacteria Alteromonadales 0.001333333 0.009812179 3.2935E-05 8.0491E-05 Burkholderia sp. HB1 Unreported Bacteria Burkholderiales 0.001333333 0.017742596 3.6033E-05 5.7848E-05 Pseudomonas sp. M30-35 Unreported Bacteria Pseudomonadales 0.001 0.038017275 3.4487E-05 5.3646E-05 Sphingobium cloacae Unreported Bacteria Sphingomonadales 0.001 0.005524192 6.7440E-05 9.5878E-05 Magnetospira sp. QH-2 Unreported Bacteria Rhodospirillales 0.001 0.046354417 6.4865E-05 8.4158E-05 Zoogloeaceae bacteirum Par-f-2 Unreported Bacteria Rhodocyclales 0.001 0.024741144 6.8570E-05 9.7871E-05

Table S8. Species identified by random forests analysis of shotgun sequencing data that exhibit significant differences in their representation in the fecal microbiomes between each two groups of mice.

(f) Species discriminating fecal microbiota of the Soil and SS mice. Mean importance of species identified by random forest are shown in the 5th column. Random forests assigns an importance score to each species by estimating the increase in error caused by removing that species from the set of predictors. In our analysis, we considered a species to be “highly predictive” if its importance score was at least 0.001. T-test was performed for the relative abundances of each species between the two groups of mice. P-values were at least 0.05 to be considered statistically significant.

Microbiological Taxonomy Random Forests P-Value Mean of relative abundance Species Microbiological Function (T-Test) Classification Bacterial Order Importance Score Soil SS Rhodococcus rhodochrous Engineered strain Bacteria Corynebacteriales 0.001333333 0.010582125 3.3232E-05 2.6478E-05 Rhodococcus sp. 2G Engineered strain Bacteria Corynebacteriales 0.001333333 0.000553061 1.9325E-05 1.0261E-05 Corynebacterium simulans Engineered strain Bacteria Corynebacteriales 0.002 0.000582373 1.0879E-04 6.8727E-05 Glaesserella parasuis Engineered strain Bacteria Pasteurellales 0.002 0.00823151 8.1456E-05 5.5468E-05 Ehrlichia muris Engineered strain Bacteria Rickettsiales 0.001333333 0.004576168 2.8483E-05 1.4534E-05 Alteromonas naphthalenivorans Engineered strain Bacteria Alteromonadales 0.003333333 0.007054149 2.0747E-05 4.6645E-05 Leptospirillum ferriphilum Engineered strain Bacteria Nitrospirales 0.001 0.023096609 1.7627E-05 2.9208E-05 Saccharomyces eubayanus Engineered strain Fungi 0.001 0.001500276 3.8904E-05 5.2286E-05 Massilia sp. NR 4-1 Antibiotic Bacteria Burkholderiales 0.001333333 0.0027257 1.3564E-04 1.0270E-04 Pathogany (no infecting mice) Bacteria Burkholderiales 0.001333333 0.015999045 5.0841E-05 1.1622E-05 Trichophyton benhamiae Pathogany (no infecting mice) Fungi 0.001333333 0.001513009 6.9469E-05 4.3698E-05 Mythimna separata entomopoxvirus Pathogany (no infecting mice) Fungi 0.001333333 0.003443534 2.3838E-05 1.6228E-05 Pathogany (no infecting mice) Bacteria Rickettsiales 0.001 0.026821298 2.5109E-05 1.4667E-05 Pandoraea sputorum Pathogany (no infecting mice) Bacteria Burkholderiales 0.001 0.020633342 4.2747E-05 2.1627E-05 Eimeria mitis Pathogany (no infecting mice) Parasite 0.004666667 0.001332273 1.0075E-04 1.4599E-04 Tenacibaculum dicentrarchi Pathogany (no infecting mice) Bacteria Flavobacteriales 0.0016 0.000220175 4.2487E-05 8.4693E-05 Corynebacterium provencense Pathogany (no infecting mice) Bacteria Corynebacteriales 0.001333333 0.02692099 3.6797E-05 5.0547E-05 Coccidioides posadasii Pathogany (no infecting mice) Fungi 0.001333333 0.030205705 2.8026E-05 3.4381E-05 Spiroplasma apis Pathogany (no infecting mice) Bacteria Entomoplasmatales 0.001 0.00015683 1.5126E-05 3.7762E-05 Neisseria sicca Pathogany (no infecting mice) Bacteria Neisseriales 0.001 0.000631674 3.2341E-05 7.4479E-05 Plasmodium coatneyi Pathogany (no infecting mice) Parasite 0.001 0.00163333 5.6831E-05 8.3291E-05 Toxoplasma gondii Pathogany (no infecting mice) Parasite 0.001 0.046180812 2.0887E-04 2.7327E-04 Gentian Kobu-sho-associated virus Pathogany (no infecting mice) Virus 0.001 0.00703728 3.3993E-08 2.6725E-07 Methylocystis sp. SC2 Unreported Bacteria Rhizobiales 0.003 0.001434621 6.5801E-05 4.7164E-05 Streptomyces sp. HNM0039 Unreported Bacteria Streptomycetales 0.002 0.000843875 8.3485E-05 4.7670E-05 Mycolicibacterium thermoresistibile Unreported Bacteria Corynebacteriales 0.002 0.000918883 7.3501E-05 3.4614E-05 Sphingomonas sp. JJ-A5 Unreported Bacteria Sphingomonadales 0.002 0.006101757 1.2273E-04 8.0568E-05 Brevundimonas naejangsanensis Unreported Bacteria Caulobacterales 0.002 0.000134175 4.7554E-05 2.5112E-05 Corynebacterium stationis Unreported Bacteria Corynebacteriales 0.001333333 0.016398551 4.7221E-04 2.3464E-05 Corynebacterium maris Unreported Bacteria Corynebacteriales 0.001333333 0.001088436 4.1778E-05 2.5833E-05 Corynebacterium glaucum Unreported Bacteria Corynebacteriales 0.001333333 0.004595581 5.8409E-05 2.9961E-05 Nocardia soli Unreported Bacteria Corynebacteriales 0.001333333 0.003416588 7.9105E-05 4.5489E-05 Pseudopropionibacterium propionicum Unreported Bacteria Propionibacteriales 0.001333333 0.007532859 1.1934E-04 7.0575E-05 Candidatus Planktophila lacus Unreported Bacteria Candidatus Nanopelagicales 0.001333333 0.022276365 2.5123E-05 1.5954E-05 Pseudomonas sabulinigri Unreported Bacteria Pseudomonadales 0.001333333 0.004700033 5.7174E-05 3.1226E-05 Psychrobacter sp. PRwf-1 Unreported Bacteria Pseudomonadales 0.001333333 0.011753859 4.1590E-05 8.2772E-06 Erythrobacter litoralis Unreported Bacteria Sphingomonadales 0.001333333 0.03410551 8.7910E-05 6.6619E-05 Paraburkholderia rhizoxinica Unreported Bacteria Burkholderiales 0.001333333 0.000459107 5.8008E-05 3.3888E-05 Azoarcus sp. KH32C Unreported Bacteria Rhodocyclales 0.001333333 0.045212688 6.3903E-05 5.0222E-05 Coniosporium apollinis Unreported Fungi 0.001333333 0.007510929 6.2199E-05 5.3713E-05 Streptomyces sp. RTd22 Unreported Bacteria Streptomycetales 0.001 0.006846255 1.2422E-04 7.4213E-05 Streptomyces formicae Unreported Bacteria Streptomycetales 0.001 0.003095186 1.0389E-04 7.4849E-05 Cellulosimicrobium cellulans Unreported Bacteria Micrococcales 0.001 0.008880177 4.3033E-05 2.8950E-05 Mycoplasma pneumoniae Unreported Bacteria Mycoplasmataceae 0.001 0.041514135 1.1351E-05 9.1170E-06 Deinococcus swuensis Unreported Bacteria Deinococcales 0.001 0.040716055 1.4601E-04 8.3000E-05 Klebsiella quasivariicola Unreported Bacteria Enterobacterales 0.001 0.013321123 6.3775E-05 4.5695E-05 Pseudomonas granadensis Unreported Bacteria Pseudomonadales 0.001 0.02342776 1.5390E-05 8.6772E-06 Pseudomonas asplenii Unreported Bacteria Pseudomonadales 0.001 0.021415514 1.8678E-05 1.3613E-05 Stenotrophomonas sp. ZAC14D2_NAIMI4_7 Unreported Bacteria Xanthomonadales 0.001 0.006056153 4.1025E-05 2.1433E-05 Stenotrophomonas sp. LM091 Unreported Bacteria Xanthomonadales 0.001 0.001554134 6.5822E-05 3.8215E-05 Lysobacter maris Unreported Bacteria Xanthomonadales 0.001 0.007007414 5.2717E-05 4.0694E-05 Colwellia sp. PAMC 21821 Unreported Bacteria Alteromonadales 0.001 0.042609245 3.8604E-05 2.3947E-05 Bradyrhizobium lablabi Unreported Bacteria Rhizobiales 0.001 0.018217331 1.8442E-04 1.3809E-04 Blastochloris viridis Unreported Bacteria Rhizobiales 0.001 0.022445626 5.2821E-05 4.1245E-05 Thermocrinis albus Unreported Bacteria Aquificales 0.001 0.003105847 3.2967E-05 1.1509E-05 Edwardsiella hoshinae Unreported Bacteria Enterobacterales 0.003 0.001036052 4.9408E-05 7.7865E-05 Fluoribacter dumoffii Unreported Bacteria Legionellales 0.002333333 0.012255638 1.8110E-05 2.9180E-05 Petrotoga mobilis Unreported Bacteria Petrotogales 0.002333333 3.08401E-05 8.2640E-05 1.5038E-04 Serpula lacrymans Unreported Fungi 0.002333333 0.002578653 4.1721E-05 5.8874E-05 Bacillus sp. WP8 Unreported Bacteria Bacillales 0.002 0.000737878 1.1782E-05 2.8083E-05 Luteipulveratus mongoliensis Unreported Bacteria Micrococcales 0.002 0.009364502 4.7012E-05 5.5909E-05 Oscillatoria nigro-viridis Unreported Bacteria Oscillatoriales 0.002 4.61338E-05 5.1116E-05 8.4941E-05 Pseudomonas sp. URMO17WK12:I11 Unreported Bacteria Pseudomonadales 0.002 0.000893523 4.9128E-05 8.8924E-05 Thermotoga sp. 2812B Unreported Bacteria Thermotogales 0.002 0.000121599 1.8954E-05 3.7638E-05 Candidatus Saccharibacteria oral taxon TM7x Unreported Bacteria Unreported 0.002 0.000123056 4.8994E-05 8.7460E-05 Aspergillus glaucus Unreported Fungi 0.0018 0.009287438 4.2318E-05 5.8542E-05 Chloroherpeton thalassium Unreported Bacteria Chlorobiales 0.001333333 0.011566105 5.9682E-05 7.7607E-05 Kushneria konosiri Unreported Bacteria Oceanospirillales 0.001333333 0.026164989 3.4409E-05 4.4284E-05 endosymbiont of Culex quinquefasciatus Unreported Bacteria Rickettsiales 0.001333333 0.030816681 3.1294E-06 6.4125E-06 Lactobacillus virus LP65 Unreported Virus 0.001333333 0.009492181 3.3993E-08 1.9656E-06 Staphylococcus cohnii Unreported Bacteria Bacillales 0.001 0.0011474 6.8347E-05 1.1235E-04 Mycobacterium paraintracellulare Unreported Bacteria Corynebacteriales 0.001 0.014841639 4.2332E-05 6.6891E-05 Gloeocapsa sp. PCC 7428 Unreported Bacteria Chroococcales 0.001 0.001786203 2.2891E-05 4.2352E-05 Elizabethkingia ursingii Unreported Bacteria Flavobacteriales 0.001 0.021794827 3.5255E-05 5.0946E-05 Unreported Bacteria Flavobacteriales 0.001 0.029539175 1.2483E-04 1.5812E-04 Gilvibacter sp. SZ-19 Unreported Bacteria Flavobacteriales 0.001 0.012262689 9.6572E-05 1.4226E-04 Pedobacter cryoconitis Unreported Bacteria Sphingobacteriales 0.001 0.011464806 7.7153E-05 9.7350E-05 Pedobacter steynii Unreported Bacteria Sphingobacteriales 0.001 0.000327501 1.0791E-04 1.4838E-04 Idiomarina piscisalsi Unreported Bacteria Alteromonadales 0.001 0.008770931 8.9738E-06 1.3136E-05 Komagataeibacter nataicola Unreported Bacteria Rhodospirillales 0.001 0.014757126 3.4312E-05 5.2628E-05 Polynucleobacter duraquae Unreported Bacteria Burkholderiales 0.001 0.011500524 1.1458E-05 1.8283E-05 Punctularia strigosozonata Unreported Fungi 0.001 0.040907548 5.3433E-05 7.1944E-05 Haloarcula hispanica Unreported Archaea 0.001 0.004099167 3.8084E-06 9.0202E-06 Sulfitobacter phage phiCB2047-B Unreported Virus 0.001 0.042521375 9.9309E-08 7.1083E-07