Gut bacterial communities ferment non-digestible carbohydrates and as a metabolic output produce short-chain fatty acids (SCFAs) that are involved in fiber’s beneficial effects. Activities of SCFAs include not only providing an energy substrate to colonocytes, but also mitigating inflammation, regulating weight through increasing satiety and balancing blood sugar, among others. Although deficiency in SCFA production has been related to chronic diseases including type 2 diabetes mellitus (T2DM), it is unknown whether gut microbiota-mediated mechanisms could actively mediate dietary fiber’s metabolic effects.
A new randomized clinical trial, led by Dr. Chenhong Zhang from the State Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology at Shanghai Jiao Tong University (Shanghai, China), has found that promotion of a select group of gut bacteria by a diet high in diverse fibers may lead to better blood glucose and lipid control and greater weight loss in people with T2DM.
The researchers randomized patients with clinically diagnosed T2DM into two groups: the treatment group (n = 27) was given a large amount of diverse fibers from dietary sources and the control group (n = 16) received standard patient education and dietary recommendations based on the 2013 Chinese Diabetes Society Guidelines for T2DM. The daily energy and macronutrient intake were similar across groups. Both groups took the drug acarbose to help control blood glucose. Dynamics of the gut microbiota and subjects’ glucose homeostasis were characterized at days 0, 28, 56, and 84.
A greater reduction in the level of haemoglobin A1c (HbA1c) was achieved in the intervention group from day 28 until the end of the study. Besides this, the proportion of participants who achieved adequate glycemic control (HbA1c < 7%) at the end of the intervention at 3 months was also higher in the intervention group. The treatment group also showed greater reduction in body weight and better blood lipid profiles when compared to the control group. These data show that a high-fiber diet improves clinical outcomes related to glucose homeostasis in participants with T2DM.
In order to determine causality between the gut microbiota and fiber-induced improvement of host glycemic control, pre- and postintervention gut microbiota from participants was transplanted into germ-free mice. Although mice transplanted with the postintervention gut microbiota from either the intervention or control group showed better metabolic health parameters than those with the preintervention gut microbiota, mice that received postintervention gut microbiota from the intervention group had the lowest fasting and postprandial blood glucose levels.
Regarding the impact of increased dietary fibers on the global structure of the gut microbiota, both groups had a significant reduction in gene richness along with significant clinical improvements from day 0 to day 28, which contradicts the current concept that greater overall diversity implies better health. After day 28, gene richness tended to be higher in the intervention group and this trend was related with better clinical outcomes related to glucose homeostasis.
When exploring functional changes in the gut microbiota involved in improved clinical outcomes, carbohydrate-active enzyme (CAZy)-encoding gene richness was decreased in both groups compared with the baseline but remained higher in the intervention group after day 28. Specifically, the intervention group showed changes in the capacity for carbohydrate metabolism, such as an enrichment of specific genes encoding a multienzyme complex for plant cell wall degradation. These results highlight that the abundance distribution of specific functional genes rather that global gene richness may be more relevant as a health-related gut microbiota profile. Besides this, different responses of SCFA-functional genes to the high-fiber intervention were detected: faecal acetic acid concentrations were similar in both groups during the whole study, whereas butyric acid concentrations increased significantly only in the intervention group.
Of the 141 strains of SCFA-producing gut bacteria identified by next-generation sequencing, only 15 strains belonging to Firmicutes, Actinobacteria and Proteobacteria phyla were promoted by consuming a high fiber diet and the response was strain-specific. All 15 positive responders in the intervention group harboured genes for acetate production and butyrate production, whereas in the control group only 3 acetate producing strains among the 15 positive responders were promoted. The effect of the high-fiber diet on promoting the butyrate production pathway and inducing butyrate production was observed only in the intervention group. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in HbA1c levels, partly through increased glucagon-like peptide-1 production. Furthermore, positive responders diminished the bacterial production of metabolically detrimental compounds such as indole and hydrogen sulphide.
Seven positive responders in the intervention group of active producers for SCFA production showed at least one significant correlation with clinical parameters. The acetate-producing Bifidobacterium pseudocatenulatum was one of the most significant promoted SCFA producers and it alleviated high-fat diet-induced dysregulation of glucose homeostasis in mice.
To sum up, dietary fiber is able to promote specific SCFA producing bacteria that may present a novel approach for managing T2DM. These results open the possibility that targeting specific gut microbial communities through dietary fiber could become an important part of T2DM treatment.
Zhao L, Zhang F, Ding X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018; 359(6380):1151-6. doi: 10.1126/science.aao5774.