Nicotinamide mononucleotide reduces metabolic-syndrome-associated lens stiffening and gut microbiota–metabolic–ocular changes in mice
Abstract
IntroductionLens stiffening contributes to impaired accommodation and age-related optical dysfunction, but whether metabolic syndrome (MetS) accelerates this biomechanical change in association with microbiota-linked metabolic disturbances remains unclear. This study evaluated whether nicotinamide mononucleotide (NMN) reduces lens stiffening in mice with diet-induced metabolic syndrome and whether changes in gut microbial metabolites, systemic inflammatory markers, and ocular biochemical injury accompany this response.MethodsMale and female C57BL/6J mice were fed a high-fat/high-sucrose regimen and assigned to vehicle, NMN dose, antibiotic-depletion, NMN plus antibiotic-depletion, and fecal microbiota transfer arms. A total of 96 mice were randomized, and 94 mice contributed valid week-16 lens stiffness measurements. The primary endpoint was lens apparent Young’s modulus. Secondary endpoints included Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), serum triglyceride, fecal microbiota diversity, fecal short-chain fatty acids, serum lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), lens nicotinamide adenine dinucleotide (NAD+), oxidative and glycation-related injury, and molecular fibrosis-associated lens markers.ResultsCompared with controls, metabolic-syndrome mice showed higher HOMA-IR, serum triglyceride, serum LPS, serum TMAO, lens malondialdehyde (MDA), lens advanced glycation end-products (AGEs), and lens apparent Young’s modulus, with lower fecal butyrate and lens NAD+. Lens apparent Young’s modulus increased from 7.4 ± 1.3 kPa in controls to 17.9 ± 2.1 kPa in metabolic-syndrome mice. NMN reduced lens stiffness to 14.8 ± 2.0 kPa at 150 mg/kg/day and 11.9 ± 2.4 kPa at 300 mg/kg/day. Fecal butyrate increased from 8.1 ± 1.9 μmol/g in metabolic-syndrome mice to 12.0 ± 2.4 μmol/g and 13.7 ± 2.8 μmol/g in the two NMN groups, while lens NAD+ increased from 1.50 ± 0.28 to 1.96 ± 0.31 pmol/mg and 2.34 ± 0.35 pmol/mg, respectively. Antibiotic depletion weakened but did not abolish the high-dose NMN ocular response, and fecal transfer from NMN-treated donors partially shifted microbial metabolite and lens stiffness endpoints toward the direct NMN-treatment profile.DiscussionThese findings support an NMN-associated reduction in metabolic-syndrome-related lens stiffening accompanied by coordinated systemic metabolic, microbial-metabolite, and ocular biochemical changes; the microbiota-related component appeared contributory rather than sufficient to explain the ocular response.
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BibTeX
@article{feng2026nicotinamide,
title = {{Nicotinamide mononucleotide reduces metabolic-syndrome-associated lens stiffening and gut microbiota–metabolic–ocular changes in mice}},
author = {Qiting Feng and Wanying Song and Lai Wei and Quan Liu},
journal = {Frontiers in Microbiology},
year = {2026},
month = nov,
doi = {10.3389/fmicb.2026.1939489},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1939489},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Nicotinamide mononucleotide reduces metabolic-syndrome-associated lens stiffening and gut microbiota–metabolic–ocular changes in mice
AU - Qiting Feng
AU - Wanying Song
AU - Lai Wei
AU - Quan Liu
PY - 2026
DA - 2026/11/02
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1939489
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1939489
AB - IntroductionLens stiffening contributes to impaired accommodation and age-related optical dysfunction, but whether metabolic syndrome (MetS) accelerates this biomechanical change in association with microbiota-linked metabolic disturbances remains unclear. This study evaluated whether nicotinamide mononucleotide (NMN) reduces lens stiffening in mice with diet-induced metabolic syndrome and whether changes in gut microbial metabolites, systemic inflammatory markers, and ocular biochemical injury accompany this response.MethodsMale and female C57BL/6J mice were fed a high-fat/high-sucrose regimen and assigned to vehicle, NMN dose, antibiotic-depletion, NMN plus antibiotic-depletion, and fecal microbiota transfer arms. A total of 96 mice were randomized, and 94 mice contributed valid week-16 lens stiffness measurements. The primary endpoint was lens apparent Young’s modulus. Secondary endpoints included Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), serum triglyceride, fecal microbiota diversity, fecal short-chain fatty acids, serum lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), lens nicotinamide adenine dinucleotide (NAD+), oxidative and glycation-related injury, and molecular fibrosis-associated lens markers.ResultsCompared with controls, metabolic-syndrome mice showed higher HOMA-IR, serum triglyceride, serum LPS, serum TMAO, lens malondialdehyde (MDA), lens advanced glycation end-products (AGEs), and lens apparent Young’s modulus, with lower fecal butyrate and lens NAD+. Lens apparent Young’s modulus increased from 7.4 ± 1.3 kPa in controls to 17.9 ± 2.1 kPa in metabolic-syndrome mice. NMN reduced lens stiffness to 14.8 ± 2.0 kPa at 150 mg/kg/day and 11.9 ± 2.4 kPa at 300 mg/kg/day. Fecal butyrate increased from 8.1 ± 1.9 μmol/g in metabolic-syndrome mice to 12.0 ± 2.4 μmol/g and 13.7 ± 2.8 μmol/g in the two NMN groups, while lens NAD+ increased from 1.50 ± 0.28 to 1.96 ± 0.31 pmol/mg and 2.34 ± 0.35 pmol/mg, respectively. Antibiotic depletion weakened but did not abolish the high-dose NMN ocular response, and fecal transfer from NMN-treated donors partially shifted microbial metabolite and lens stiffness endpoints toward the direct NMN-treatment profile.DiscussionThese findings support an NMN-associated reduction in metabolic-syndrome-related lens stiffening accompanied by coordinated systemic metabolic, microbial-metabolite, and ocular biochemical changes; the microbiota-related component appeared contributory rather than sufficient to explain the ocular response.
SN - 1664-302X
ER -