Short chain fructo-oligosaccharides (scFOS) are a mixture of oligosaccharides consisting of glucose linked to fructose units; links between fructose units are β-(1,2) 1. They are produced commercially from sucrose using an enzymatic process. ScFOS are poorly digested in the human small intestine but are fermented in the colon by the resident microflora 2.

In light of the recent interest in "prebiotics", defined as "a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or the activity of one or a limited number of bacterial species in the colon" 3, it has been shown in humans that addition to the diet of short-chain fructo-oligosaccharides (scFOS) at doses of from 4 to 12.5 g/d leads to an increase in faecal bifidobacteria counts 45. Such bifidobacteria-promoting dietary interventions can be perceived as beneficial, since bifidobacteria are a saccharolytic genus and could contribute to the same type of protection that breast-feeding provides against gut infections 6, while also playing a role in the prevention of colorectal carcinogenesis 45.

In a recent study comprising 200 healthy volunteers, we determined the bifidogenic properties of 7 non-digestible carbohydrates administered at a dose of 10 g/d in the human diet : Four non-digestible carbohydrates were found to be statistically different from placebo, i.e. bifidogenic, at 10 g/d: scFOS, soybean-oligosaccharides, galacto-oligosaccharides and type III resistant starch; we therefore performed a dose-response relationship analysis of these 4 substrates at doses ranging from 2.5 to 10 g/d and compared them to a placebo 7. The effects of the 7-day treatment period were found to be significantly different among the 4 non-digestible carbohydrates (P = 0.009). A trend was found for the doses tested (P= 0.06) suggesting that the relationship between dose and bifidobacteria count could be different among the 4 non-digestible carbohydrates, and that among them, a dose-response effect could be present. Since we previously demonstrated a dose-response relationship between scFOS and bifidobacteria at higher doses 5, we considered it of interest to investigate a possible dose-response relationship between scFOS and bifidobacteria at lower doses.

This placebo-controlled dose-response study shows that 7 days of ingestion of scFOS at a dose of 2.5 to 10 g/d, which was well tolerated, led to a significant increase in faecal bifidobacteria in healthy volunteers. This is the first study to demonstrate the bifidogenic effect of sc-FOS with such a low dose (2.5 g/d). Moreover, it must be stressed that the increase in bifidobacteria counts was correlated with the dose of ingested scFOS. We previously reported such an effect in healthy volunteers in another dose-response relationship study. However, the optimal and well-tolerated dose of scFOS leading to a significant increase in faecal bifidobacteria under usual diet was 10 g/d. These differences are probably due to the relatively small size of each sample, which decreased the power of the study. The increase in total anaerobes observed at the dose of 10 g/d is probably due to the high stimulation of colonic microflora induced by prebiotics 89. The faecal bifidobacteria and anaerobe levels observed in this study were similar to those found in previous studies 35 in healthy volunteers on scFOS.

ScFOS has been studied extensively and its bifidogenic effects demonstrated in well-controlled human trials 3458. However, Roberfroid et al. concluded from a compilation work that in a large population, there seems to be no dose-response effect of these non-digestible carbohydrates on bifidobacteria for daily intake doses between 4 and 40 g/d 10. Here, we found a linear dose-response relationship from 2.5 to 10 g/d, suggesting a dose-effect relationship. Such a relationship has been previously found in a study with scFOS, in which the range of doses was wider, from 5 to 20 g/d 8, and in another trial using a mixture of galacto- and fructooligosaccharides as supplementation of term infant formula 11. It was not found with other substrates such as galacto-oligosaccharides alone, resistant starch or soybean oligosaccharides 7.

We did not find any significant reduction in any other genus. There is little published data in humans available in the literature for comparison. Contradictory results have been reported in this field; while Gibson et al. 3 showed a significant reduction in Bacteroides using 15 g/d oligofructose, Rao 9 found an increase in Bacteroides using oligofructose at dose of 5 g/d. Moreover using oligofructose at 8 g/d, 2 authors did not find any effect on Bacteroide 712. The reasons for these discrepancies are unclear.

A decrease in colonic pH could reduce the risk of developing colonic cancer, since an inverse correlation between stool pH and colon cancer risk was observed 1314. Slight acidification of faecal contents during scFOS ingestion was observed in animals 15 and in humans 12. In our previous studies, faecal pH did not change during ingestion of scFOS 58. However, as the faecal pH is the net sum of the degree of short-chain fatty acid absorption and bicarbonate secretion during passage through the colon, faecal pH does not reflect the pH in the colon under physiological conditions 1617.

Symptoms relating to gas production in the gut are widely reported in human prebiotic feeding studies but nevertheless remain very mild at the recommended intake levels 1819. Compared to placebo, we did not find any significant digestive intolerance symptoms except minor bloating with scFOS. Similarly, no dose-response relationship for digestive symptoms was observed. In a threshold study to evaluate symptomatic response to varying levels of scFOS ingested regularly by 14 healthy volunteers, excessive flatus and borborygmi were reported by about 10% of volunteers at 10 g/d of scFOS, and excessive flatus, borborygmi and bloating were recorded for about 20–30% of volunteers at 20 g/d 20. In another study in which 10 volunteers ingested 15 g/d FOS for 12 days, gaseous symptoms such as abdominal cramps, excess flatus and bloating were all significantly more severe in subjects ingesting the FOS than in control subjects ingesting sucrose (P < 0.05) 21. However, with the exception of flatulence, these symptoms, if present, were usually mild, and did not increase (or decrease) during the course of the 12-day period. In our previous study comprising 10 healthy volunteers who ingested 12.5 g/d of scFOS for 12 days, only bloating was found to be significantly more frequent during the scFOS ingestion period than during placebo ingestion (P < 0.05), but this was very mild and present in only 5/10 volunteers 5. From all these results, it appears that the most common symptoms noted during scFOS administration are excess flatus and/or bloating, but only a minority of subjects experiences them and they are usually very mild.

This study confirmed that scFOS is bifidogenic and well tolerated in healthy volunteers. A bifidogenic effect appeared for the first time at 2.5 g/d of scFOS, and a dose-response relationship was demonstrated from 2.5 to 10 g/d.

Yoram Bouhnik, Laurent Raskine, Guy Simoneau: no affiliations Damien Paineau, Francis Bornet: Nutri-Health SA, Rueil-Malmaison, France

YB participated in the study design, the data collection, the data analysis and he drafted the manuscript. LR carried out the data collection. GS participated in the data collection and analysis. DP participated in the writing of the manuscript. FB conceived of the study and participated in the writing of the manuscript. All authors read and approved the final manuscript.