Although most dietary amino acids and peptides are absorbed in the small intestine, substantial amounts can enter the large intestine. In humans, colonocytes have the capacity for amino acid absorption because amino acid transporters are present in the large intestine, but the absorption of nutritionally relevant amounts of indispensable amino acids and peptides in the human large intestine has not been convincingly demonstrated.

Current direct and quantitative evidence on amino acid absorption in the human colon is minimal. The colon is an effective bioreactor with auxotrophic microbiota that can hydrolyze dietary and endogenous protein and synthesize essential amino acids through nitrogen salvage, but the net contribution to the host remains uncertain.

In healthy adults consuming cooked, dehulled faba beans, "The ileal N digestibility was 84.1% ± 7.7%." It further reports that "The ileal digestibility of individual AAs varied from 85.1% ± 13.7% for histidine to 94.2% ± 3.6% for Glx." The authors note that "The mean digestibility of individual AAs was ∼6 percentage points higher than the digestibility of nitrogen, reaching 89.8% ± 5.9%, whereas the mean IAA digestibility was 88.0% ± 7.3%." They conclude that "Protein ileal digestibility of cooked, dehulled faba beans in humans was moderate (<85%), but that of AAs was close to 90%."

This comparative study states that seven protein sources were selected "that spanned the range of digestibilities typically seen in foods (the determined true ileal mean AA digestibility values ranged from 60% to 98%)." It reports that a regression of human versus pig true ileal amino acid digestibility gave the equation "y = 1.00x – 0.010," indicating close agreement between species. The authors conclude: "True ileal AA digestibility values determined in the growing pig can be directly used for predicting digestibility in adult humans," implying that, across tested foods, the majority of ingested amino acids are absorbed before the terminal ileum.

It is estimated that around 6–18 g of protein could reach the large intestine daily, where it becomes available for bacterial proteolysis and subsequent fermentation. Under typical conditions, AA-fermenting microbes constitute only a minor subset of coliform bacteria, accounting for less than 1% of the total population. Despite their small numbers, these microbes exhibit considerable diversity. Clostridia and Peptostreptococci are the most commonly isolated bacteria in media that use AAs as sources of energy and carbon.

This methods-focused review explains that "True ileal digestibility is calculated by correcting apparent ileal digestibility for endogenous amino acid losses, thereby reflecting the proportion of dietary amino acids absorbed before the distal ileum." In an example comparing two proteins in humans, it reports that "The calculated mean true ileal amino acid digestibility coefficients for zein were 0.63 and 0.60 and for WPI were 0.92 and 0.95," indicating that high-quality proteins can reach around 90–95% true ileal amino acid digestibility. The article emphasizes that ileal digestibility better captures amino acids absorbed before they enter the colon, where they may otherwise be metabolized by microbiota.

The PubMed abstract for this human ileal balance study reports: "The ileal digestibility of individual AAs varied from 85.1% ± 13.7% for histidine to 94.2% ± 3.6% for glutamine + glutamate. The mean AA digestibility was ∼6 percentage points higher than the digestibility of N, reaching 89.8% ± 5.9%, whereas indispensable AA digestibility was 88.0% ± 7.3%." It concludes that "Protein ileal digestibility of cooked, dehulled faba beans in humans was moderate (<85%), but that of AAs was close to 90%." These values imply that only about 10–15% of dietary amino acids from this legume protein remain unabsorbed by the ileum under the studied conditions.

With usual mixed diets, apparent digestibility of dietary protein in the small intestine is generally high, often exceeding 90%. Consequently, only a relatively small proportion of ingested protein escapes digestion and absorption in the small intestine and enters the large intestine. The majority of amino acids present in the lumen of the small intestine are absorbed and appear in the portal blood, where they are available for metabolism by the liver and other tissues.

This human and pig study reports that "not all free AAs are fully absorbed by the end of the small intestine." It quantifies that for a high‑quality protein such as whey, which was ">95%" bioavailable, if the free amino acids present in ileal digesta were absorbed they would only increase bioavailability by about "0.4%-unit" in humans and "0.1%-unit" in pigs. For a low‑bioavailability protein (zein, ~70% bioavailability), the contribution of unabsorbed free amino acids would increase apparent AA bioavailability by only a few percentage points, showing that the fraction of free AAs escaping small‑intestinal absorption is small in absolute terms for normal, high‑quality proteins.

This study examined whether amino acids released into the hindgut (i.e. not absorbed in the small intestine) significantly affect measures of small‑intestinal absorption kinetics. The authors conclude that applying a correction for amino acids appearing in the hindgut "did not affect" the estimated kinetics of disappearance in the small intestine, implying that the fraction of dietary amino acids bypassing small‑intestinal absorption and becoming available to colonic bacteria is small under the tested conditions.

It has been estimated that 12–18 g of proteinaceous material enters the human colon each day. This nitrogenous material comes from undigested dietary protein, endogenous proteins such as digestive enzymes and sloughed epithelial cells, and mucus. Studies using ileostomists have suggested that 10–20% of dietary protein may escape digestion in the small intestine and enter the large bowel. Once in the colon, proteins are degraded by bacterial enzymes to peptides and amino acids, which are then fermented to a range of metabolites including ammonia, short-chain fatty acids, branched-chain fatty acids, phenols and indoles.

This article reports that normal adults ingest roughly 70–100 g of dietary protein daily, but because of endogenous secretions, about 2–3 times this amount enters the small intestinal lumen. It states that "more than 95%" of this protein is digested and absorbed in the small intestine under normal conditions, leaving only a small fraction to enter the colon, where it becomes substrate for bacterial fermentation and growth.

This systematic review on protein digestion in humans states that in healthy subjects with intact gastrointestinal tracts, "overall true ileal digestibility of high-quality animal proteins (e.g., milk, egg, meat) is generally high, often above 90%." The authors describe that most ingested amino acids are absorbed in the small intestine and that significant malabsorption or increased delivery of protein to the colon is mainly observed in pathological conditions or after bariatric surgery. This implies that under normal physiological conditions, only a relatively small fraction of dietary amino acids typically escapes absorption in the small intestine.

This paper explains that the small intestine has a high capacity for nitrogen and amino acid uptake, with most luminal amino acids being absorbed and then extensively metabolized in the splanchnic bed. It also notes that only a relatively small amount of nitrogen passes into the large intestine, where it is used by the microflora, reinforcing the concept that bacterial consumption occurs mainly on a small residual pool of amino acids and peptides that escaped small‑intestinal absorption.

The chapter states that "Most of this mixture of exogenous and endogenous proteins (115 to 200 g/day) is efficiently digested and taken up by the absorptive enterocytes as free amino acids and dipeptides and tripeptides." It quantifies that "Around 85% of the total protein is absorbed anterior to the end of the small intestine (terminal ileum), with around 10 to 20 g of protein entering the colon each day." It further notes that daily fecal nitrogen losses are about the equivalent of 10 g protein and that this unabsorbed nitrogen is "used in the large intestine by the microflora for growth and is therefore mainly present in the feces as part of the bacterial mass," indicating that colonic bacteria consume much of the small fraction that escapes absorption.

This review on colonic protein fermentation notes: "Only a small proportion of dietary protein and peptides normally escape digestion and absorption in the small intestine and reach the large intestine." It further explains that the amount of substrate available for colonic bacteria "is increased when protein intake is very high or when digestive capacity is impaired." Under usual dietary conditions in healthy individuals, it describes the colonic protein load as limited, leading to relatively modest amino acid loss via bacterial metabolism compared with the total amount ingested.

This review reports that in healthy adults, "the majority of dietary proteins are digested and absorbed as amino acids and small peptides in the small intestine, with overall true ileal digestibility values for most animal proteins typically exceeding 90%." It notes that factors such as plant anti-nutritional components can reduce digestibility, but under normal conditions, the fraction of intact amino acids reaching the colon is relatively small. Any amino acids that enter the colon are rapidly utilized by microbiota, leading to nitrogenous metabolites excreted in feces and urine, but this represents a minor proportion of total ingested amino acids in healthy individuals consuming mixed diets.

Under normal physiological conditions, the small intestine is highly efficient in absorbing amino acids derived from dietary and endogenous proteins. More than 90% of luminal amino acids are absorbed in the small intestine of most species. Only a small proportion of amino acids and peptides passes into the large intestine, where they can be used by microbiota or excreted.

This extension resource defines key digestibility measures: "Ileal digestibility: measured by the difference between the amount of amino acids ingested and the amount of amino acids recovered from the digesta in the ileum." It further distinguishes "Apparent ileal digestibility (AID): measured by the difference between the amount of amino acids ingested and the amount of amino acids recovered from the digesta in the ileum without considering the endogenous amino acid losses." It notes that "True ileal digestibility (TID)" corrects for both basal and specific endogenous losses, meaning TID reflects the fraction of dietary amino acids that disappear from the lumen prior to the terminal ileum rather than being available to colonic bacteria.

In this study of healthy adults consuming meat-based diets, the authors measured true ileal amino acid digestibility using ileal effluent collections. They found that true ileal digestibility coefficients for indispensable amino acids from beef and pork were generally high, often in the range of 90–95%, with overall mean values above 90%. The paper notes that these high coefficients indicate efficient small-intestinal absorption of dietary amino acids from meat and that only a relatively minor proportion of ingested amino acids is present in the ileal effluent available to enter the colon under normal conditions.

In ileostomy subjects consuming a low-protein diet, endogenous nitrogen flow at the terminal ileum averaged 1.8 g N/d, corresponding to approximately 11 g endogenous protein. Dietary nitrogen malabsorption was small, averaging 0.3 g N/d or about 2 g protein. These results indicate that most of the nitrogen entering the colon in these conditions is of endogenous origin rather than undigested dietary protein.

When dietary protein intake is within the normal range, only a limited amount of undigested protein and peptides reaches the colon due to the high efficiency of small-intestinal digestion and absorption. However, when protein intake is very high or carbohydrate intake is low, the amount of protein entering the colon increases. This leads to increased bacterial fermentation of amino acids and increased production of potentially toxic metabolites such as ammonia, hydrogen sulfide and N-nitroso compounds.

Functional amino acids, including glutamine, arginine, glycine, glutamic acid, and tryptophan, have been reported to improve intestinal growth and ameliorate intestinal injury. The editorial is relevant mainly as context for amino-acid roles in intestinal physiology, not as direct evidence on normal colonic amino-acid loss.

In healthy adults, most dietary protein is digested and absorbed in the small intestine, leaving only small residual amounts to reach the colon under normal conditions. Colonic bacteria can metabolize unabsorbed protein and amino acids, but the fraction reaching the colon is usually low in a normal mixed diet.