Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice.

Dimet-Wiley A, Wu Q, Wiley JT, Eswar A, Neelakantan H, Savidge T, Watowich S

Scientific reports10 Jan 2022Cited by 5 (Europe PMC)

PMID35013352PMCIDPMC8748953DOI10.1038/s41598-021-03670-5PepBankPUB-35013352

Summary

Treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with low-fat diet (LD) promoted dramatic whole-body adiposity and weight loss in diet-induced obese (DIO) mice, rapidly normalizing these measures to age-matched lean animals, while LD switch alone was unable to restore these measures to age-matched controls in the same time frame. Since mouse microbiome profiles often highly correlate with body weight and fat composition, this study was designed to test whether the cecal microbiomes of DIO mice treated with NNMTi and LD were comparable to the microbiomes of age-matched lean counterparts and distinct from microbiomes of DIO mice maintained on a high-fat Western diet (WD) or subjected to LD switch alone. There were minimal microbiome differences between lean and obese controls, suggesting that diet composition and adiposity had limited effects. However, DIO mice switched from an obesity-promoting WD to an LD (regardless of treatment status) displayed several genera and phyla differences compared to obese and lean controls. While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar. K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts; these genera are tied to body weight and metabolic regulation. Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites' abundances. Collectively, these results provide a novel foundation for future investigations.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In obese mice switched to low-fat diet, NNMT inhibition decreased Erysipelatoclostridium relative abundance compared with vehicle.
In plain wordsIn obese mice switched to low-fat diet, NNMT inhibition decreased Erysipelatoclostridium abundance compared with vehicle.
Peptide
5-amino-1MQ
Outcome
DecreaseErysipelatoclostridium relative abundance
Study
mousen: not reported in source
diet-induced obese mice
Comparator
vehicle-treated low-fat diet counterparts
Outcome group
Gut microbiota · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts
Show in the study text Report a problemFND-3501335204
02AnimalAnimal study (in vivo)Efficacy outcome
In obese mice switched to low-fat diet, NNMT inhibition increased Lactobacillus relative abundance compared with vehicle.
In plain wordsIn obese mice switched to low-fat diet, NNMT inhibition increased Lactobacillus abundance compared with vehicle.
Peptide
5-amino-1MQ
Outcome
IncreaseLactobacillus relative abundance
Study
mousen: not reported in source
diet-induced obese mice
Comparator
vehicle-treated low-fat diet counterparts
Outcome group
Gut microbiota · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts
Show in the study text Report a problemFND-3501335205

Studies that did not test the peptide alone5

In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking 5-amino-1MQ.

03AnimalNot a test of 5-amino-1MQ aloneAnimal study (in vivo)Efficacy outcome
In obese mice, low-fat diet switching changed microbial genera and phyla regardless of NNMT inhibitor treatment compared with obese and lean controls.
In plain wordsIn mice, low-fat diet switching changed microbial genera and phyla regardless of NNMT inhibitor treatment compared with obese and lean controls.
Peptide
5-amino-1MQ
Outcome
MixedMicrobial genera and phyla
Study
mousen: not reported in source
diet-induced obese mice
Comparator
obese and lean controls
Outcome group
Gut microbiota · Gastrointestinal
Source sentences
Summary
However, DIO mice switched from an obesity-promoting WD to an LD (regardless of treatment status) displayed several genera and phyla differences compared to obese and lean controls.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-3501335201
04AnimalNot a test of 5-amino-1MQ aloneAnimal study (in vivo)Efficacy outcome
In mice, alpha diversity did not significantly differ among study groups, including NNMT inhibitor-treated mice.
In plain wordsIn mice, microbial alpha diversity did not significantly differ among groups, including NNMT inhibitor-treated mice.
Peptide
5-amino-1MQ
Outcome
No significant changeAlpha diversity
Study
mousen: not reported in source
diet-induced obese mice
Comparator
other study groups
Outcome group
Gut microbiota · Gastrointestinal
Source sentences
Summary
While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-3501335202
05AnimalNot a test of 5-amino-1MQ aloneAnimal study (in vivo)Efficacy outcome
In mice, beta diversity analysis suggested that mice within each treatment group had the most similar microbiomes.
In plain wordsIn mice, beta diversity analysis suggested that microbiomes were most similar within the same treatment group.
Peptide
5-amino-1MQ
Outcome
Not applicableBeta diversity
Study
mousen: not reported in source
diet-induced obese mice
Outcome group
Gut microbiota · Gastrointestinal
Source sentences
Summary
While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-3501335203
06AnimalNot a test of 5-amino-1MQ aloneAnimal study (in vivo)Efficacy outcome
In mice, Parasutterella abundance increased in both vehicle- and NNMT inhibitor-treated low-fat diet groups compared with controls.
In plain wordsIn mice, Parasutterella abundance increased in both vehicle- and NNMT inhibitor-treated low-fat diet groups compared with controls.
Peptide
5-amino-1MQ
Outcome
IncreaseParasutterella relative abundance
Study
mousen: not reported in source
diet-induced obese mice
Comparator
controls
Outcome group
Gut microbiota · Gastrointestinal
Source sentences
Summary
Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites' abundances.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-3501335206
07AnimalNot a test of 5-amino-1MQ aloneAnimal study (in vivo)Mechanism
In mice, Parasutterella relative abundance significantly correlated with several adipose tissue metabolite abundances.
In plain wordsIn mice, Parasutterella abundance was linked to several adipose tissue metabolite abundances.
Peptide
5-amino-1MQ
Outcome
Not applicableParasutterella association with adipose metabolites
Study
mousen: not reported in source
diet-induced obese mice
Outcome group
Gut microbiota · Gastrointestinal
Source sentences
Summary
Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites' abundances.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-3501335207

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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