TY - JOUR
T1 - Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity
AU - Qiu, Xiaoxue
AU - Macchietto, Marissa G.
AU - Liu, Xiaotong
AU - Lu, You
AU - Ma, Yiwei
AU - Guo, Hong
AU - Saqui-Salces, Milena
AU - Bernlohr, David A.
AU - Chen, Chi
AU - Shen, Steven
AU - Chen, Xiaoli
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/1
Y1 - 2021/1
N2 - Lipocalin 2 (Lcn2), as an antimicrobial peptide is expressed in intestine, and the upregulation of intestinal Lcn2 has been linked to inflammatory bowel disease. However, the role of Lcn2 in shaping gut microbiota during diet-induced obesity (DIO) remains unknown. We found that short-term high fat diet (HFD) feeding strongly stimulates intestinal Lcn2 expression and secretion into the gut lumen. As the HFD feeding prolongs, fecal Lcn2 levels turn to decrease. Lcn2 deficiency accelerates the development of HFD-induced intestinal inflammation and microbiota dysbiosis. Moreover, Lcn2 deficiency leads to the remodeling of microbiota-derived metabolome, including decreased production of short-chain fatty acids (SCFAs) and SCFA-producing microbes. Most importantly, we have identified Lcn2-targeted bacteria and microbiota-derived metabolites that potentially play roles in DIO and metabolic dysregulation. Correlation analyses suggest that Lcn2-targeted Dubosiella and Angelakisella have a novel role in regulating SCFAs production and obesity. Our results provide a novel mechanism involving Lcn2 as an antimicrobial host factor in the control of gut microbiota symbiosis during DIO.
AB - Lipocalin 2 (Lcn2), as an antimicrobial peptide is expressed in intestine, and the upregulation of intestinal Lcn2 has been linked to inflammatory bowel disease. However, the role of Lcn2 in shaping gut microbiota during diet-induced obesity (DIO) remains unknown. We found that short-term high fat diet (HFD) feeding strongly stimulates intestinal Lcn2 expression and secretion into the gut lumen. As the HFD feeding prolongs, fecal Lcn2 levels turn to decrease. Lcn2 deficiency accelerates the development of HFD-induced intestinal inflammation and microbiota dysbiosis. Moreover, Lcn2 deficiency leads to the remodeling of microbiota-derived metabolome, including decreased production of short-chain fatty acids (SCFAs) and SCFA-producing microbes. Most importantly, we have identified Lcn2-targeted bacteria and microbiota-derived metabolites that potentially play roles in DIO and metabolic dysregulation. Correlation analyses suggest that Lcn2-targeted Dubosiella and Angelakisella have a novel role in regulating SCFAs production and obesity. Our results provide a novel mechanism involving Lcn2 as an antimicrobial host factor in the control of gut microbiota symbiosis during DIO.
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U2 - 10.1038/s41366-020-00712-2
DO - 10.1038/s41366-020-00712-2
M3 - Article
C2 - 33214705
AN - SCOPUS:85096331280
SN - 0307-0565
VL - 45
SP - 143
EP - 154
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 1
ER -