Impact of the lipase inhibitor orlistat on the human gut microbiota

Yudai Uehira; Hiroaki Ueno; Junki Miyamoto; Ikuo Kimura; Yohei Ishizawa; Hiroshi Iijima; Shota Muroga; Toru Fujita; Soichi Sakai; Yoshishige Samukawa; Yuri Tanaka; Shinya Murayama; Hideyuki Sakoda; Masamitsu Nakazato

doi:10.1016/j.orcp.2023.08.005

Impact of the lipase inhibitor orlistat on the human gut microbiota

Obes Res Clin Pract. 2023 Sep-Oct;17(5):411-420. doi: 10.1016/j.orcp.2023.08.005. Epub 2023 Sep 9.

Authors

Affiliations

¹ Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
² Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo 183-8509, Japan.
³ Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
⁴ DNA Chip Research Inc., Minato-ku, Tokyo 105-0022, Japan.
⁵ Taisho Pharmaceutical Co., Ltd., Toshima-ku, Tokyo 170-8633, Japan.
⁶ Department of Bioregulatory Sciences, Faculty of Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
⁷ Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan; Department of Bioregulatory Sciences, Faculty of Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
⁸ Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan; Department of Bioregulatory Sciences, Faculty of Medicine, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan; Department of Inter-organ Communication Research Project, Frontier Science Research Center, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan; Institute for Protein Research, Osaka University, Osaka 565-0871, Japan. Electronic address: nakazato@med.miyazaki-u.ac.jp.

PMID: 37679239
DOI: 10.1016/j.orcp.2023.08.005

Abstract

Orlistat, an anti-obesity agent, inhibits the metabolism and absorption of dietary fat by inactivating pancreatic lipase in the gut. The effect of orlistat on the gut microbiota of Japanese individuals with obesity is unknown. This study aimed to explore the effects of orlistat on the gut microbiota and fatty acid metabolism of Japanese individuals with obesity. Fourteen subjects with visceral fat obesity (waist circumference ≥85 cm) took orlistat orally at a dose of 60 mg, 3 times a day for 8 weeks. Body weight; waist circumference; visceral fat area; levels of short-chain fatty acids, gut microbiota, fatty acid metabolites in the feces, and gastrointestinal hormones; and adverse events were evaluated. Body weight, waist circumference, and blood leptin concentrations were significantly lower after orlistat treatment (mean ± standard deviation, 77.8 ± 9.1 kg; 91.9 ± 8.7 cm; and 4546 ± 3211 pg/mL, respectively) compared with before treatment (79.4 ± 9.0 kg; 94.4 ± 8.0 cm; and 5881 ± 3526 pg/mL, respectively). Significant increases in fecal levels of fatty acid metabolites (10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid, and 10-oxo-trans-11-octadecenoic acid) were detected. Meanwhile, no significant changes were found in abdominal computed tomography parameters, blood marker levels, or short-chain fatty acid levels in the feces. Gut microbiota analysis revealed that some study subjects had decreased abundance of Firmicutes, increased abundance of Bacteroidetes, and increased α-diversity indices (Chao1 and ACE) after 8 weeks of treatment. The levels of Lactobacillus genus and Lactobacillus gasseri were significantly higher after 8 weeks of treatment. None of the subjects discontinued treatment or experienced severe adverse events. This study suggested that orlistat might alter gut microbiota composition and affect the body through fatty acid metabolites produced by the modified gut bacteria.

Keywords: Fatty acid metabolites; Gut microbiota; Lipase inhibitor; Obesity; Orlistat.

MeSH terms

Body Weight
Fatty Acids
Gastrointestinal Microbiome*
Humans
Lipase
Obesity
Orlistat / pharmacology

Substances

Orlistat
Fatty Acids
Lipase