Methotrexate effect on gut microbiota in RA patients, USA
34 samples from autoimmune/inflammatory (rheumatoid arthritis) adult and elderly patients in the USA, studying gut microbiota response to methotrexate drug therapy in an intervention design. machine-written summary
34 samples · 34 runs · US · Adult · 2021 · 4.55 Gbp / sample
Checked this project's papers and archive records yourself? Mark it human-verified.
what each source gave
| ✓ Sequence archive | 408 sample values (collection date, country, health condition, health condition detail, intervention, intervention detail, latitude, location region) |
| ○ Abstract / description | read; no usable statement |
| ✓ Full text | 34 sample values (location site) · PMC7954989 |
| ○ Supplementary tables | files read; no table could be matched to the samples |
| ✓ External resources | 102 sample values (age, antibiotic exposure, sex) · from curatedMetagenomicData 3 (cMD 3) |
| – User contribution | nothing uploaded yet |
| – Human verified | not yet checked by a person · I checked this project — verify it |
intervention · arms resolved
17 people have samples in more than one arm.
Non-antibiotic pharmaceutical given as the study intervention (metformin design single_arm_before_after · population autoimmune_inflammatory · Methotrexate treatment in RA patients, pre- vs post-treatment microbiota
“RA patient microbiotas were sensitive to MTX” — abstract:33440172 (study level; per-sample arms are in the intervention column below)
longitudinal
17 of 17 people sampled more than once (34 samples; median 2, up to 2 per person) · follow-up median 30 d (max 30 d) · median interval between samples 30 d (time from timepoint numbers, unit from the stated sampling schedule). Schedule stated by the source: “Two timepoints per patient: day 0 (naive/pre-treatment) and day 30 (post-MTX treatment)”.
Each row is one person (17 shown); dots are samples at days since that person's first sample.
Genera, mean relative abundance over 32 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).
| field | samples | coverage | R1 | R2 | R3 | R4 |
|---|---|---|---|---|---|---|
| age_category | 34 | 100% | ||||
| country | 34 | 100% | 34 | |||
| health_condition | 34 | 100% | 34 | |||
| subject_id | 34 | 100% | 34 | |||
| age_at_collection_days | 34 | 100% | 34 | |||
| antibiotic_exposure | 34 | 100% | 34 | |||
| collection_date | 34 | 100% | 34 | |||
| detailed_location | 34 | 100% | ||||
| health_condition_detail | 34 | 100% | 34 | |||
| intervention | 34 | 100% | 34 | |||
| intervention_detail | 34 | 100% | 34 | |||
| latitude | 34 | 100% | 34 | |||
| location_region | 34 | 100% | 34 | |||
| location_site | 34 | 100% | 34 | |||
| longitude | 34 | 100% | 34 | |||
| sex | 34 | 100% | 34 | |||
| timepoint_label | 34 | 100% | 34 | |||
| medication | 17 | 50% | 17 | |||
| medication_detail | 17 | 50% | 17 |
- Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation. 2021 PMID 33440172 PMC7954989 own_data
Archive description
Here, we show that the first-line rheumatoid arthritis (RA) drug methotrexate (MTX) broadly alters the human gut microbiota. Drug sensitivity varied between strains. Growth experiments, transcriptomics, and metabolomics suggest that the mechanism of action is conserved between mammalian and bacterial cells. RA patient microbiotas were sensitive to MTX and changes in gut bacterial taxa and gene family abundance were distinct between responders and non-responders. Transplantation of post-treatment samples into germ-free mice given an inflammatory trigger led to reduced immune activation relative to pre-treatment controls, enabling the identification of MTX-modulated bacterial taxa associated with intestinal and splenic immune cells. These results show how conservation in cellular pathways across domains of life can result in broad off-target effects of drugs on the human gut microbiota with downstream consequences for immune function.
How this project entered the registry
Classified as human gut / stool shotgun DNA metagenome of adult by sonnet_x2 with confidence 0.75. Assay shotgun_dna.
- host study.title · “human gut microbiota”
- body site run.scientific_name · “gut metagenome”
- life stage study.description · “rheumatoid arthritis (RA) drug methotrexate”
Evidence examples (one per field × route)
| sample | field | value | route | conf. | source | quote |
|---|---|---|---|---|---|---|
| SAMN15823258 | age_at_collection_days | 10227.0 | R2 | 0.75 | external.cmd source | age: 28; age_unit: (empty); age_group: Adult |
| SAMN15823258 | antibiotic_exposure | no | R2 | 0.75 | external.cmd source | antibiotics_current_use: No |
| SAMN15823258 | collection_date | 2014-01 | R1 | 0.90 | biosample.attribute:collection_date | 2014-01 |
| SAMN15823258 | country | US | R1 | 0.90 | sample.attr.geo_loc_name | USA |
| SAMN15823258 | health_condition | autoimmune_inflammatory | R1 | 0.70 | sample.name_rule:alias | NYU_RA_5B |
| SAMN15823258 | health_condition_detail | RA | R1 | 0.70 | sample.name_rule:alias | NYU_RA_5B |
| SAMN15823258 | intervention | no_intervention | R1 | 0.90 | biosample.attribute:treatment | treatment: naive |
| SAMN15823258 | intervention_detail | treatment-naive, pre-methotrexate | R1 | 0.90 | biosample.attribute:treatment | treatment: naive |
| SAMN15823258 | latitude | 40.7468 | R1 | 0.90 | biosample.attribute:lat_lon | 40.7468 N 73.9723 W |
| SAMN15823258 | location_region | New York | R1 | 0.60 | biosample.attribute:lat_lon | 40.7468 N 73.9723 W |
| SAMN15823258 | location_site | NYU Langone Medical Center rheumatology clinics | R3 | 0.70 | paper.fulltext.methods | New York University Langone Medical Center’s rheumatology clinics and offices |
| SAMN15823258 | longitude | -73.9723 | R1 | 0.90 | biosample.attribute:lat_lon | 40.7468 N 73.9723 W |
| SAMN15823259 | medication | immunosuppressant_or_biologic | R1 | 0.90 | biosample.attribute:treatment | MTX |
| SAMN15823259 | medication_detail | MTX | R1 | 0.90 | biosample.attribute:treatment | MTX |
| SAMN15823258 | sex | female | R2 | 0.75 | external.cmd source | sex: Female |
| SAMN15823258 | subject_id | 005 | R1 | 0.85 | sample.attr.patient_id | 005 |
| SAMN15823258 | timepoint_label | 0 | R1 | 0.85 | sample.attr.day | 0 |
Sequencing
34 runs over 34 samples · mean 4.41 Gbp per run (median 4.55 Gbp, total 150.02 Gbp; 34 runs with a base count) · layout PAIRED 34 · platform ILLUMINA 34 · models Illumina NovaSeq 6000 (34) · 94% of runs with a Sandpiper profile · first public 2021-01-11
Authors (9)
Nayak RR first · Alexander M · Deshpande I · Stapleton-Gray K · Rimal B · Patterson AD · Ubeda C · Scher JU · Turnbaugh PJ last
Downloads
PRJNA656577.csv.gz (2.2 KB) · parquet (73.8 KB) — all 34 samples, every field with route and confidence · PRJNA656577_determinations.csv.gz (5.8 KB) — 544 evidence rows