The same dose of short chain fatty acids did different things depending on where in the gut it landed

Each participant attended three visits and received a single 230 mmol dose of short chain fatty acids targeted to the small intestine, the same dose targeted to the colon, or placebo, with blood sampled for 8 hours afterwards.

PYY release was greater after colonic delivery, with an estimated difference of 111.46 pg/mL per hour (95% CI 4.33 to 218.59, p=0.04).

GLP-1 release went the other way. It was higher after small intestinal delivery by 16.00 pM per hour (95% CI 1.31 to 30.68, p=0.03), which the authors flag as unexpected.

Circulating short chain fatty acids were far higher after small intestinal delivery: acetate by 360.33 uM per hour (95% CI 226.50 to 494.17, p<0.001), propionate by 18.00 (95% CI 11.62 to 24.49, p<0.001) and butyrate by 7.21 (95% CI 3.77 to 10.66, p<0.001). Glucose and c peptide showed no effect of delivery site.

The numbers

PYY, colonic vs small intestinal	111.46 pg/mL/h, 95% CI 4.33 to 218.59, p=0.04
GLP-1, small intestinal vs colonic	16.00 pM/h, 95% CI 1.31 to 30.68, p=0.03
Circulating acetate, small intestinal vs colonic	360.33 uM/h, 95% CI 226.50 to 494.17, p<0.001
Circulating butyrate, small intestinal vs colonic	7.21 uM/h, 95% CI 3.77 to 10.66, p<0.001
Glucose and c peptide	no effect of delivery site

Why this might happen

Proposed by the authors This is the explanation the authors offer in their discussion. This study did not test it.

The authors set out two predictions before the trial. Small intestinal cells do not metabolise short chain fatty acids, so delivering there should push more into the bloodstream. Enteroendocrine cell density is lower in the small intestine, so hormone release should be smaller there.

The first prediction held convincingly. Systemic acetate, propionate and butyrate were all far higher after small intestinal delivery.

The PYY half held too, with more released after colonic delivery, as the density argument predicts.

The GLP-1 result broke the pattern and the authors say so, describing it as unexpected without offering a resolving explanation in the abstract. The discussion is not openly reachable, so we do not know what they went on to argue.

Drawn from Abstract, full text behind a publisher block.

What this does not show

It does not show that eating fibre does any of this. A single 230 mmol bolus delivered by a targeted capsule is a pharmacological intervention. Habitual fibre fermentation produces short chain fatty acids slowly, across a day, in amounts this study does not model.
It does not show anyone ate less. Appetite was measured on visual analogue scales. There was no food intake, energy balance or body weight endpoint.
The hormone signal did not reach metabolism. Glucose and c peptide showed no effect of delivery site, so the endocrine differences did not translate into a measurable glycaemic difference over 8 hours.
It does not apply to the people this matters most for. Twenty eight healthy adults. No participants with obesity, prediabetes, diabetes or altered gut transit.

Where this leaves us

Short chain fatty acids can no longer be treated as one intervention with one effect. Where they are released changes which hormone answers, and one of the two answers contradicted the standing anatomical explanation.

Twenty eight healthy adults given a single targeted dose, measured over 8 hours.

Repeating the delivery comparison in people with obesity or impaired glucose control, with food intake rather than a rating scale as the outcome, would show whether any of this changes eating.

Caveats worth holding

PubMed records the online date as 10 August and Crossref records 11 August. The earlier date is used here.
The full text is behind a publisher block, so the mechanistic reading comes from the abstract rather than the discussion.
Single acute dose, healthy adults, no chronic arm.
Volume and issue are not yet assigned.