Perinatal phlorizin alleviates maternal high-fat diet-induced metabolic syndrome in female mouse offspring: role of gut microbiota
In C57BL/6 mice, perinatal maternal phlorizin (0.8 g/kg diet) intervention favored glucolipid metabolism and gut microbiota composition in adult female offspring exposed to maternal high-fat diet, with effects transmissible via FMT to antibiotic-treated male recipients.
| Population | Female offspring of C57BL/6 mice whose mothers received a high-fat diet during gestation and lactation |
|---|---|
| Intervention | Perinatal phlorizin (0.8 g/kg diet) co-administered to the mother during gestation and lactation |
| Comparator | Female offspring of high-fat diet mothers without phlorizin; offspring of standard diet mothers as additional control |
| Outcome | Glucolipid metabolism (adult female offspring); Gut microbiota composition (Firmicutes/Bacteroidetes ratio); Fecal SCFAs and serum GLP-1/2; Intestinal barrier integrity; Obesity susceptibility after dietary challenge; Microbial mediation via FMT (ABX males); Insulin resistance |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Glucolipid metabolism (adult female offspring) | Direction: PHZ vs HFD favored; in the extractable numeric effect size or 95% CI reported | — | Very low | — | 1 studies |
| Gut microbiota composition (Firmicutes/Bacteroidetes ratio) | Direction: PHZ reduced ratio vs HFD; in the extractable numeric effect size or 95% CI reported | — | Very low | — | 1 studies |
| Fecal SCFAs and serum GLP-1/2 | Direction: PHZ elevated both vs HFD; in the extractable numeric effect size or 95% CI reported | — | Very low | — | 1 studies |
| Intestinal barrier integrity | Direction: PHZ improved vs HFD; in the extractable numeric effect size or 95% CI reported | — | Very low | — | 1 studies |
| Obesity susceptibility after dietary challenge | Direction: PHZ reduced susceptibility vs HFD; in the extractable numeric effect size or 95% CI reported | — | Very low | — | 1 studies |
| Microbial mediation via FMT (ABX males) | Direction: PHZ-FMT attenuated MS vs HFD-FMT in ABX males; in the extractable numeric effect size or 95% CI reported | — | Very low | — | 1 studies |
| Insulin resistance | Direction: PHZ reduced insulin resistance vs HFD; in the extractable numeric effect size or 95% CI reported | — | Very low | — | 1 studies |
Context
Maternal obesity programs offspring for metabolic syndrome via transgenerational mechanisms under the DOHaD hypothesis. Perinatal nutritional interventions targeting gut microbiota may interrupt this programming. Phlorizin, an SGLT1/2 inhibitor found in apples, has demonstrated metabolic benefits in adult models, but its transgenerational potential was unknown.
What the study showed
Maternal high-fat diet induced dysbiosis (increased Firmicutes/Bacteroidetes ratio), insulin resistance, and impaired intestinal barrier in adult female offspring without overt obesity. Perinatal phlorizin co-intervention reversed these parameters, increased Akkermansia muciniphila and Blautia sp. abundance, elevated fecal SCFAs and serum GLP-1/2, and reduced obesity susceptibility after dietary challenge. FMT from phlorizin-intervened female offspring to ABX male mice attenuated metabolic syndrome induced by FMT from HFD offspring. Absolute numbers and 95% CI were not provided in the available text.
How it was done
Experimental study in C57BL/6 mice; mothers received high-fat diet ± phlorizin (0.8 g/kg) during gestation and lactation. Female offspring were assessed at weaning and in adulthood for metabolic parameters, microbiota (16S rRNA), SCFAs, GLP-1/2, and intestinal barrier. Obesogenic challenge and FMT in antibiotic-treated males were used to confirm microbial mediation. Sample size and exact number of animals per group are not reported in the available abstract.
Effect magnitude
The text does not report extractable effect sizes with 95% CI; effects are described qualitatively/semi-quantitatively ('significantly increased', 'restored') without absolute values comparable between groups in the provided text.
Risk of bias
Preclinical murine model study; direct extrapolation to humans is not supported. Sample size, number of animals per group, and formal risk-of-bias tools (RoB) are not reported in the available text. The use of ABX males as FMT recipients to 'eliminate estrogenic effects' is methodologically unconventional and introduces additional confounders (antibiotic-induced dysbiosis, sex difference). The phlorizin dose (0.8 g/kg diet) is pharmacokinetically distant from viable human doses.
What this study does NOT prove
This study does not prove that perinatal phlorizin prevents transgenerational metabolic syndrome in humans. It does not establish definitive mechanistic causality nor demonstrate fetal safety of the intervention in any species beyond C57BL/6 mice.
In clinical practice
This study does not support clinical recommendation of perinatal phlorizin in humans. Clinicians should interpret findings as hypothesis-generating. Perinatal interventions to modulate transgenerational microbiota lack adequate clinical evidence.
Limitations
Preclinical murine model study; direct extrapolation to humans is not supported. Sample size, number of animals per group, and formal risk-of-bias tools (RoB) are not reported in the available text. The use of ABX males as FMT recipients to 'eliminate estrogenic effects' is methodologically unconventional and introduces additional confounders (antibiotic-induced dysbiosis, sex difference). The phlorizin dose (0.8 g/kg diet) is pharmacokinetically distant from viable human doses.
What is still missing
Studies in non-human primates or clinical trials in obese pregnant women are needed to evaluate safety and efficacy of perinatal phlorizin. Identification of specific epigenetic or microbial mechanisms mediating transgenerational effects requires further investigation.
Technical appendix
Version history
- 1.0 · 2026-06-26 — Auto-generated under Evidence Standard v1.0