{"doi":"10.1002/ctm2.1053","title":"The bacterial quorum sensing peptide iAM373 is a novel inducer of sarcopenia","abstract":"Dear Editor, Sarcopenia - the accelerated loss of muscle mass, strength and function with ageing – represents an important health challenge with reduced quality of life and increased mortality.1 Gut microbiota has been suggested to contribute to this age-associated muscle wasting but the underlying mechanisms are still unclear.2 Here, we uncover the quorum sensing peptide iAM373 as a hitherto unknown contributor to sarcopenia. In vitro screening has shown that several bacterial quorum sensing molecules can impact C2C12 murine muscle cells, with iAM373 (SIFTLVA), a quorum sensing peptide (QSP) produced by E. faecalis, decreasing C2C12 myoblast metabolic activity measured by MTT assays.3 Because one of the hallmarks of sarcopenia is a decrease in metabolic activity, we used a stepwise translational approach to evaluate and confirm the relevance of iAM373 in sarcopenia (Figure 1A). Initially, MTT concentration-response experiments in murine and human myoblasts as well as in myotubes were performed. We found that iAM373 decreased metabolic activity in a concentration-dependent manner in both murine and human myoblasts and myotubes (Figure 1B and Figure S1). The minimal inhibitory concentrations (IC10) for iAM373 to exert these effects were in the pico-to-nanomolar range: 61 pM (human) and 282 pM (murine) in myotubes, 35 nM (human) and 10 nM (murine) in myoblasts (cfr. Table S1 for IC50 values). Based on the in vitro results, we examined whether iAM373 is able to induce a sarcopenia phenotype in vivo. We used C. elegans to study sarcopenia in vivo as these animals exhibit a sarcopenia phenotype with age that can be measured in an automated manner.4, 5 Incubation of C. elegans worms with iAM373 (1 μM) during 3 days induced a sarcopenia phenotype (Figure 1C,D and Figure S2). The rationale for using this concentration can be found in Text S1. To evaluate the amino acid specificity, we conducted C. elegans experiments with a scrambled iAM373 derivative. These experiments confirmed the effects of iAM373 on C. elegans mobility as well as demonstrated the primary structure specificity of the observed effects (Figure S3). Next, we assessed the presence of iAM373 in murine and human plasma. Therefore, we developed a bioanalytical method using reversed-phase ultra-high-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer (RP-UHPLC-TQ-MS). Positive samples were confirmed using RP-UHPLC coupled to a time-of-flight mass spectrometer (RP-UHPLC-TOF-MS). Method suitability characteristics of this bioanalytical method can be found in Tables S2–4. In a cohort of 25 adults (age, 28 ± 9.3 years; female, 44%), two positive samples were identified (Figure 1E,F). Their estimated concentrations were 16.7 and 77.3 pM. Five of the 25 adults were again sampled on another day – four of them were iAM373 negative on both occasions and one was positive on both occasions (16.7 and 16.0 pM), suggesting low day-to-day variation. From a cohort of 15 mice (age, 5 months; male, 100%), one positive sample (1.0 nM) was identified. These findings indicate that iAM373 can be detected in mammalian plasma, and represent the first demonstration of a QSP in human plasma. The presence of iAM373 was in the same order of magnitude (±10% positive) as other QSPs and non-peptide QSMs in murine and human plasma respectively.6, 7 Moreover, as we expect that iAM373 can be present in human plasma for years, the anticipated muscle exposures (time x concentration) are similar to the iAM373 exposures causing an effect in the in vitro and C. elegans in vivo experiments. To explore a possible association between the presence of iAM373 and sarcopenia, we recruited fifty-one residents of an assisted living centre for older people and assessed the presence of iAM373 in plasma as well as skeletal muscle mass, grip strength and walking speed (cfr. Online methods). The main characteristics of the study cohort are presented in Table S5. Of the 51 residents (age, 83 ± ","journal":"Clinical and Translational Medicine","year":2022,"id":253826,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":679772,"name":"Evelien Wynendaele","orcid":"0000-0003-0969-7580","position":1,"is_corresponding":false},{"id":899878,"name":"Amélie Descamps","orcid":"0000-0003-2694-4643","position":2,"is_corresponding":false},{"id":679771,"name":"Nathan Debunne","orcid":"0000-0001-5839-7539","position":3,"is_corresponding":false},{"id":725999,"name":"Bart P. Braeckman","orcid":"0000-0002-0085-8264","position":4,"is_corresponding":false},{"id":899879,"name":"Marjan De Mey","orcid":"0000-0002-8134-9436","position":5,"is_corresponding":false},{"id":900355,"name":"Julie Coudenys","orcid":null,"position":6,"is_corresponding":false},{"id":900356,"name":"Liesbeth Crombez","orcid":null,"position":7,"is_corresponding":false},{"id":899880,"name":"Frederick Verbeke","orcid":"0000-0002-3737-7405","position":8,"is_corresponding":false},{"id":899881,"name":"Yorick Janssens","orcid":"0000-0002-7353-5300","position":9,"is_corresponding":false},{"id":890151,"name":"Rekin’s Janky","orcid":"0000-0001-5135-2469","position":10,"is_corresponding":false},{"id":899882,"name":"Evy Goossens","orcid":"0000-0001-6476-5932","position":11,"is_corresponding":false},{"id":900357,"name":"Caroline Vlaeminck","orcid":null,"position":12,"is_corresponding":false},{"id":899883,"name":"Dries Duchi","orcid":"0000-0002-7891-2400","position":13,"is_corresponding":false},{"id":899884,"name":"Vanessa Andries","orcid":"0009-0002-2233-723X","position":14,"is_corresponding":false},{"id":444323,"name":"Émilie Dumas","orcid":"0000-0002-4528-9229","position":15,"is_corresponding":false},{"id":899885,"name":"Mirko Petrović","orcid":"0000-0002-7506-8646","position":16,"is_corresponding":false},{"id":899886,"name":"Tom Van de Wiele","orcid":"0000-0001-6854-5689","position":17,"is_corresponding":false},{"id":899887,"name":"Daniel Knappe","orcid":"0000-0002-4661-8979","position":18,"is_corresponding":false},{"id":880938,"name":"Ralf Hoffmann","orcid":"0000-0001-9932-5646","position":19,"is_corresponding":false},{"id":175178,"name":"Vincent Mouly","orcid":"0000-0003-3809-4033","position":20,"is_corresponding":false},{"id":678430,"name":"Anne Bigot","orcid":"0000-0003-0337-5425","position":21,"is_corresponding":false},{"id":899888,"name":"Lars Vereecke","orcid":"0000-0002-1593-862X","position":22,"is_corresponding":false},{"id":899889,"name":"Filip Van Immerseel","orcid":"0000-0003-0455-3350","position":23,"is_corresponding":false},{"id":899890,"name":"Nele Van Den Noortgate","orcid":"0000-0001-5546-5380","position":24,"is_corresponding":false},{"id":899891,"name":"Bart De Spiegeleer","orcid":"0000-0001-6794-3108","position":25,"is_corresponding":false},{"id":80087,"name":"Dirk Elewaut","orcid":"0000-0002-7468-974X","position":26,"is_corresponding":false},{"id":899877,"name":"Anton De Spiegeleer","orcid":"0000-0002-3681-2807","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T00:24:59.596040Z","pmid":"36229976","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}