Prebiotics pectin and resistant starch-type 4 stimulate peptide YY and cholecystokinin to promote satiety, and improve gut microbiota composition

FASEB J. 2025 Mar 31;39(6):e70457. doi: 10.1096/fj.202403239R.

Abstract

Dietary prebiotics pectin and resistant starch type-4 (RS-4) promote satiety and alter gut microbiota; however, the underlying neurohormonal mechanisms of satiety remain poorly understood. We determined the effects of pectin, RS-4, and their combination on energy balance and gut microbiota composition, and assessed whether the gut hormones peptide YY (PYY) and cholecystokinin (CCK) play a role in fiber-induced satiety. High-fat diet -induced obese male rats (n = 7-8/group) were fed either control, pectin, RS-4, or a combination of pectin and RS-4 diet. We found that pectin, RS-4, and their combination decreased food intake. Pectin alone, or combined with RS-4, shifted substrate utilization towards fat and reduced gains in weight and adiposity. Pectin alone or combined with RS-4 enhanced the expression and plasma concentrations of PYY and CCK. Importantly, systemic blockade of PYY-Y2 and CCK-1 receptors attenuated the hypophagic effects of pectin, and CCK-1 receptor blockade partly attenuated the hypophagia from RS-4. The prebiotics significantly altered fecal β-diversity metrics, suggestive of improvements in gut microbiota composition. Pectin and RS-4 alone, or in combination, were associated with increased relative abundance of phylum Bacteroidota, decreased Firmicutes, and increased concentrations of amino acids and biogenic amines in feces. Collectively, these findings suggest that dietary pectin and RS-4 improved energy balance and gut microbiota composition, and importantly, demonstrated that the satiety effects of these diets were mediated, in part, via enhanced endogenous PYY and CCK signaling.

Keywords: cholecystokinin; energy balance; metabolome; microbiota; peptide YY; prebiotics.

MeSH terms

  • Animals
  • Cholecystokinin* / metabolism
  • Diet, High-Fat / adverse effects
  • Gastrointestinal Microbiome* / drug effects
  • Male
  • Obesity / metabolism
  • Pectins* / administration & dosage
  • Pectins* / pharmacology
  • Peptide YY* / metabolism
  • Prebiotics* / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Satiation* / drug effects
  • Satiety Response* / drug effects
  • Starch* / pharmacology

Substances

  • Peptide YY
  • Cholecystokinin
  • Prebiotics
  • Pectins
  • Starch