Human gut bacteria Bacteroides uniformis enhances endurance exercise performance
“Gut health” and “gut microbiota” have often been heard recently, and people have been increasingly aware of becoming healthy from their guts. Asahi Group conducted research focusing on athletes’ gut microbiota and newly found a relationship between a specific gut microbe and host’s athletic performance. Here, we present the study findings that we believe would help improve exercise performance by adjusting gut microbiota appropriate for exercise.
●The study identified that a human gut bacteria Bacteroides uniformis (B. uniformis) enhances endurance exercise performance.
●Supplementation with α-cyclodextrin (αCD), a cyclic oligosaccharide, increases the B. uniformis abundance in the human intestines and enhances endurance exercise performance.
●B. uniformis might improve endurance exercise performance by facilitating endogenous glucose production in the liver via producing short-chain fatty acids in the guts.
This study started in 2015, a historic year when Aoyama Gakuin University won the Tokyo-Hakone collegiate Ekiden road relay for the first time. At that time, the research laboratory of Asahi (then Calpis Co., Ltd.) was located next to the practice track of the track and field team (long-distance running division) of Aoyama Gakuin University, so the lab staff had interacted with the running team members for some time. This close relationship opened up the collaborative study. To conduct research, we repeatedly visited the running team’s dormitory to collect samples and tried to devise experimental systems and mechanisms while there was almost no previous research literature. With all those laborious efforts, we were filled with joy and excitement when we ultimately identified the gut bacteria associated with athletic capacity and their contribution to enhancing endurance excise performance. We are happy that this study was finally published after eight years of hard work that we had continued without giving it up. After the publication, we will continue to promote research on utilizing these bacteria as a material for foods with function claims and develop products that can deliver value to our customers.
I believe that the findings of this study have had two major academic impacts. One is that it demonstrated the effect of a gut bacterial species in a human clinical trial. As for exercise and gut environment, a study in 2019 found that abundance of Veillonella was higher in runners’ gut microbiota; however, the association between the bacteria and the improvement of exercise performance has only been verified in mouse model experiments. Although our study appeared to be quite similar to this approach, we demonstrated that αCD supplementation increases the B. uniformis abundance in the human guts and improves endurance exercise performance through a double-blinded randomized controlled trial, whose evidence level is the highest in human trials. This is a major achievement of our study.
The other major impact is that this study indicated that gut bacteria might help expand human functionality. Many previous studies on gut bacteria have focused on themes exploring associations between gut microbes and various diseases. Those studies take approaches, for example, which bring negative states, such as those of disease, back to zero, the healthy state, or prevent from falling into the negative states. However, we took a completely different approach that makes the zero-state positive. In this study, we found a bacterial function to improve endurance exercise performance, but gut bacteria are likely to have other hidden various abilities.
*Scheiman, J. et al. Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nature Medicine 25, 1104-1109 (2019)
We identified B. uniformis as a gut microbe characteristic of long-distance runners. We further conducted an experiment on the association between the gut microbe and endurance exercise showing that B. uniformis enhances endurance exercise performance. We also demonstrated that supplementing with αCD, which B. uniformis can readily utilize as a nutrient, improves human endurance exercise performance. The results of this study suggest that B. uniformis could enhance endurance exercise performance by promoting endogenous glucose production in the liver via producing acetic and propionic acids in the guts.
Fig. 1-1. B. uniformis abundances in the guts of the athlete group (red) and the nonathlete male control group (blue)
Fig. 1-2. Correlation between B. uniformis abundance in the guts of the athlete group and the 3000-m race time
The research group analyzed the gut microbiota of 48 male athletes belonging to the track and field team (long-distance running division) of Aoyama Gakuin University (athlete group) and 10 age-matched Japanese male nonathletes (nonathlete group). We found that the athlete group had a significantly higher abundance of Bacteroides species, than the nonathlete group.
In addition to the fact that the athlete group had a higher abundance of B. uniformis (one copy of 16S rRNA-encoding gene is defined as one bacterial cell in this study) (Fig. 1-1), we further discovered a significant negative correlation showing that athletes with a higher B. uniformis cells in the gut had shorter 3000-m race time (Fig. 1-2). These results suggest that B. uniformis might be associated with endurance exercise performance in humans (Fig. 1-2).
Fig. 2-1. Increase of the B. uniformis abundance in the guts of the αCD group
B. uniformis is one of the dominant bacterial species in the human guts. To investigate how an increase in the abundance of B. uniformis in the guts affects exercise performance in humans, we first searched for food materials that could increase the bacteria’s quantity and found αCD, a cyclic oligosaccharide, as a candidate. Then, we conducted a double-blinded, randomized controlled trial to investigate how supplementing with αCD would affect the B. uniformis abundance in the human guts and exercise performance.
Supplements containing αCD were administered to 10 Japanese healthy men with a regular exercise habit aged between 20 and 49 years for 8 weeks (αCD group). And placebo supplements, considered not to affect exercise performance, were given to another 11 men for the same weeks (placebo group). Measuring the B. uniformis abundances in the subjects’ guts after 4 weeks and 8 weeks from the start of the administration, the abundance in the αCD group after 8 weeks significantly increased from the baseline (Fig. 2-1).The abundance of B. uniformis showed no significant change in the placebo group after 4 and 8 weeks.
Fig. 2-2. Time required to pedal 10 km on an exercise bike in the αCD group
To examine the effect of αCD supplementation on exercise performance, the research team asked the subjects to pedal 10 km on an exercise bike and measured the completion time. The time required to complete pedaling in the αCD group after 4 and 8 weeks of supplementation shortened significantly compared to the time at the baseline (Fig. 2-2). In contrast, the time after 8 weeks of supplementation in the αCD group was also significantly shorter than that in the placebo group (Fig. 2-2).
Fig. 2-3. Fatigue levels after a 50-min. biking exercise session in the αCD group
The improvement in endurance exercise performance could have a secondary effect of reducing postexercise fatigue. We thus measured fatigue immediately after a 50-minute biking exercise session using a Visual Analog Scale (VAS) questionnaire and demonstrated a significant reduction in fatigue in the αCD group immediately after exercise compared to that before ingesting αCD (Fig. 2-3). The double-blinded, randomized, controlled study suggests that αCD supplementation increases the abundance of B. uniformis in the human guts, improves human endurance exercise performance, and reduces fatigue after exercise.
Fig. 3. Potential mechanism through which B. uniformis enhances endurance exercise performance
The underlying mechanism of these effects would be as follows: B. uniformis produces acetic and propionic acids from carbohydrates, such as αCD, in the guts. These short-chain fatty acids facilitate hepatic glycogenolysis and gluconeogenesis, which is biological pathways to produce glucose from compounds other than carbohydrates, mainly in the liver, during exercise. Glucose resulting from these processes is considered to be provided throughout the body as an energy source for exercise, enhancing endurance performance.
This study is the first to identify that B. uniformis, one of the dominant gut bacteria in the human microbiota, is involved in endurance exercise performance. It also demonstrated that supplementation with αCD, a cyclic oligosaccharide, enhances human endurance exercise performance. These findings suggest that prebiotics targeting B. uniformis might boost human exercise performance, indicating potential applications in the fields of sports and beverages in the future. Further investigation of other functional properties of B. uniformis is to be considered.
This study is conducted by the researchers at the Core Technology Laboratories in Asahi Quality & Innovations, Ltd. (Head Office: Ibaraki, Japan; President: Manabu SAMI), responsible for the advanced research functions in the Asahi Group, under the umbrella of the Asahi Group Holdings Ltd. (Head Office: Tokyo, Japan; President: Atsushi KATSUKI) in collaboration with Project Professor Shinji FUKUDA at the Institute for Advanced Biosciences, Keio University (then Director General: Masaru TOMITA) and Professor Yoshihide UCHIYAMA and Professor Susumu HARA at Aoyama Gakuin University (President: Hiroshi SAKAMOTO). The human clinical study of αCD was conducted after obtaining approval of an external ethical review committee.
This study was published in the international scientific journal Science Advances on January 25, 2023. Asahi Quality & Innovations, Ltd. will continue to promote “research and development to provide excellent health materials” and contribute to pursuing customers’ health maintenance and life enrichment.
Hiroto Morita, Chie Kano, Chiharu Ishii, Noriko Kagata, Takamasa Ishikawa, Akiyoshi Hirayama, Yoshihide Uchiyama, Susumu Hara, Teppei Nakamura, Shinji Fukuda. “Bacteroides uniformis and its preferred substrate, α-cyclodextrin, enhance endurance exercise performance in mice and human males." Science Advances 9.4 (2023): eadd2120.doi: 10.1126/sciadv.add2120.
※1 Gut microbiota
A cluster of microorganisms comprised mainly of bacteria living in the intestinal tracts of humans and animals. It is called gut microbiota or microbial flora because the intestinal inner surface covered with gut bacteria looks like a grassland where plants grow in clusters.
※2 Prebiotics
Food components consumed by living microorganisms that are beneficial to human health.
※3 Bacteroides uniformis
A species of anaerobic bacteria commonly living in the human intestines.
※4 α-cyclodextrin (αCD)
A type of oligosaccharide in which glucose units are cyclically chained. Supplementation with α-cyclodextrin is known to alter the composition of the gut microbiota.
※5 Short-chain fatty acids
Organic acids produced by gut bacteria, which have 6 or fewer carbon atoms, including acetic, propionic, and butyric acids. They are produced when gut microbes break down dietary fiber. These acids are considered to create a mildly acidic environment in the intestines to help suppress the growth of toxic bacteria, facilitate peristaltic movement, and control immune responses.
※6 Double-blinded, randomized, controlled study
A type of human clinical study that examines the effectiveness of the targeted food items. This type of study is conducted by dividing study subjects into a group that ingest the target food item and a group that take in placebo item, whose components are the same as those in the target food except for the test substance, without letting the people involved in the study know which subjects take in the study food item. Then, the results from the two groups are compared.
※7 VAS（visual analog scale）
This method evaluates the strength of specific feelings or emotions with a visual scale. On the questionnaire sheet, there is a black line with one end indicating the maximum level and the other end the minimum. Respondents answer the level of their feeling at the time by pointing it on the black line.
※8 Glycogen
A polysaccharide synthesized from glucose. The degradation of glycogen mainly triggers producing glucose in the liver, raising the blood glucose level.
