{"doi":"10.3389/fphys.2021.812882","title":"Human Beta Defensin 2 Ameliorated Alcohol-Associated Liver Disease in Mice","abstract":"Alcohol-associated liver disease (ALD) is a prevalent liver disorder and significant global healthcare burden with limited effective therapeutic options. The gut-liver axis is a critical factor contributing to susceptibility to liver injury due to alcohol consumption. In the current study, we tested whether human beta defensin-2 (hBD-2), a small anti-microbial peptide, attenuates experimental chronic ALD. Male C57Bl/6J mice were fed an ethanol (EtOH)-containing diet for 6 weeks with daily administration of hBD-2 (1.2 mg/kg) by oral gavage during the final week. Two independent cohorts of mice with distinct baseline gut microbiota were used. Oral hBD-2 administration attenuated liver injury in both cohorts as determined by decreased plasma ALT activity. Notably, the degree of hBD-2-mediated reduction of EtOH-associated liver steatosis, hepatocellular death, and inflammation was different between cohorts, suggesting microbiota-specific mechanisms underlying the beneficial effects of hBD-2. Indeed, we observed differential mechanisms of hBD-2 between cohorts, which included an induction of hepatic and small intestinal IL-17A and IL-22, as well as an increase in T regulatory cell abundance in the gut and mesenteric lymph nodes. Lastly, hBD-2 modulated the gut microbiota composition in EtOH-fed mice in both cohorts, with significant decreases in multiple genera including Barnesiella , Parabacteroides , Akkermansia , and Alistipes , as well as altered abundance of several bacteria within the family Ruminococcaceae. Collectively, our results demonstrated a protective effect of hBD-2 in experimental ALD associated with immunomodulation and microbiota alteration. These data suggest that while the beneficial effects of hBD-2 on liver injury are uniform, the specific mechanisms of action are associated with baseline microbiota.","journal":"Frontiers in Physiology","year":2022,"id":256096,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":905424,"name":"Ida Larsen","orcid":null,"position":1,"is_corresponding":false},{"id":491643,"name":"Josiah Hardesty","orcid":"0000-0003-1955-3046","position":2,"is_corresponding":false},{"id":535316,"name":"Ying Song","orcid":"0000-0002-0643-3718","position":3,"is_corresponding":false},{"id":491644,"name":"Dennis Warner","orcid":"0000-0002-5303-6870","position":4,"is_corresponding":false},{"id":295155,"name":"Craig J. McClain","orcid":"0000-0002-7219-8939","position":5,"is_corresponding":false},{"id":904961,"name":"Rui Sun","orcid":"0000-0002-8484-8089","position":6,"is_corresponding":false},{"id":481172,"name":"Zhongbin Deng","orcid":"0000-0003-1409-5824","position":7,"is_corresponding":false},{"id":54279,"name":"Benjamin A. H. Jensen","orcid":"0000-0001-6991-0828","position":8,"is_corresponding":false},{"id":491645,"name":"Irina Kirpich","orcid":"0000-0002-9545-6451","position":9,"is_corresponding":false},{"id":491642,"name":"Jeffrey Warner","orcid":"0000-0003-2022-7854","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T00:25:21.336200Z","pmid":"35153819","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":[]}