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Study breakdown

Probiotic Supplementation Alters Neuropeptide Y, Ghrelin, and Leptin Levels While Reducing Anxiety-Related Feeding in Rats

evidence
The takeaway

A probiotic blend increased adrenal neuropeptide Y expression, modified anxiety-related feeding behavior, and interacted with diet and sex to alter ghrelin and leptin levels in rats.

Adrenal NPY increased with probiotic

Cerebiome probiotic independently raised neuropeptide Y expression — a key stress and appetite regulatory peptide — regardless of diet or sex

What the researchers found

Cerebiome probiotic attenuated increased calorie intake in Western-diet-fed rats. Probiotic standard-diet males showed reduced anxiety in the novelty-suppressed feeding task. Probiotic rats overall had more feeding bouts in the center of the open field (suggesting less anxiety about eating in a novel environment). Probiotic administration increased adrenal neuropeptide Y (NPY) expression regardless of diet or sex. Plasma leptin was increased with Western diet; plasma ghrelin was elevated in standard-diet females. Female rats had higher adrenal glucocorticoid receptor expression than males. Effects were sex- and diet-dependent, highlighting the importance of studying both variables.

Why it matters

The gut-brain axis — how gut bacteria influence brain function — is one of the most active areas of neuroscience research. This study connects probiotics to specific peptide hormone changes (NPY, ghrelin, leptin) that regulate both anxiety and appetite. Understanding these interactions could inform probiotic-based interventions for anxiety, stress eating, and metabolic disorders, especially given the sex-specific effects that highlight the need for personalized approaches.

How the study worked

80 male and female Long-Evans rats were born to dams receiving probiotic or placebo during gestation and lactation, then continued on their respective treatments. Groups received either standard diet or a Western diet (D12079B formulation). Behavioral testing included the novelty-suppressed feeding task after 24-hour fasting. Adrenal glands were analyzed for neuropeptide Y and glucocorticoid receptor expression. Plasma leptin and ghrelin were measured at sacrifice.

What this study cannot tell us

This is a rat study, and probiotic effects may not translate directly to humans. The rats received probiotics from gestation through adulthood, making it unclear whether the effects are developmental or ongoing. Only two probiotic strains were tested in combination, so individual strain contributions can't be determined. Adrenal NPY expression was measured, not brain NPY, which may have different significance. The Western diet used is one specific formulation and may not represent all unhealthy diets.

How to read the evidence

This is a well-designed preclinical study with 80 rats across multiple conditions (2 × 2 × 2 factorial design including sex). The inclusion of both sexes and multiple outcome measures is a strength, but findings are in rats and may not translate to human probiotic use.

When this study was published

Published in 2025, this study reflects the current frontier of psychobiotic research, connecting probiotic effects to specific neuropeptide hormone changes.

The bigger picture

Probiotics are increasingly studied for mental health effects ('psychobiotics'), but the mechanisms are poorly understood. This study provides evidence that probiotics alter neuropeptide signaling — specifically NPY in adrenal glands and appetite hormones ghrelin and leptin in plasma. NPY is one of the most abundant neuropeptides in the brain and a key regulator of stress, anxiety, and appetite. The finding that probiotics modify NPY expression while also changing feeding behavior connects the microbiome to the neuroendocrine peptide systems that control both mood and metabolism.

Questions still open

  • Does the probiotic-induced increase in adrenal NPY expression contribute to stress resilience, and would brain NPY show similar changes?
  • Could targeted probiotics be developed as adjunctive treatments for anxiety disorders or stress-related eating?
  • How do the sex-specific probiotic effects translate to human populations — would women and men respond differently to psychobiotic interventions?

Common questions

How can gut bacteria affect anxiety and appetite?
Gut bacteria communicate with the brain through several pathways, including the vagus nerve and by influencing hormone production. This study showed that a specific probiotic blend changed levels of neuropeptide Y (a stress-regulating peptide) in the adrenal glands and altered anxiety-related feeding behavior. It also modified plasma levels of ghrelin (the hunger hormone) and leptin (the satiety hormone) — demonstrating that gut bacteria can directly influence the peptide hormones that control both mood and appetite.
Did the probiotic work differently for males and females?
Yes — the effects were clearly sex-dependent. Probiotic males on standard diet showed the most anxiety reduction, while ghrelin levels were specifically elevated in standard-diet females. Females also had higher adrenal glucocorticoid receptor expression overall. These sex differences are important because they suggest probiotic interventions may need to be tailored differently for men and women.

Read the original research

Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 administration to Long-Evans rats has interactive effects with sex and diet on anxiety-related feeding behaviors and specific endocrine outcomes.

Physiology & behavior, 300, 115030

Citation

Myles, Elizabeth M; O'Leary, M Elizabeth; Romkey, Isaac D; Hamm, Sara I; Dauphinee, Laura; Piano, Amanda; Bronner, Stéphane; Perrot, Tara S. (2025). Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 administration to Long-Evans rats has interactive effects with sex and diet on anxiety-related feeding behaviors and specific endocrine outcomes.. Physiology & behavior, 300, 115030. https://doi.org/10.1016/j.physbeh.2025.115030