A head-to-head trial tested whether changing what people eat could reshape the gut microbiome and influence two of the biggest treatment targets in type 2 diabetes.
Study: A high-fiber diet altered gut microbiota, improved glycemic control, and reduced body weight in people with newly diagnosed type 2 diabetes and obesity. Image Credit: Tatjana Baibakova / Shutterstock.com
In a recent study published in Frontiers in Microbiology, researchers compared the therapeutic efficacy of a high-fiber dietary intervention against standard metformin monotherapy in treating adults diagnosed with diabesity, the coexistence of type 2 diabetes mellitus (T2DM) and obesity.
Why fiber and the gut microbiome matter in diabesity
‘Diabesity’ is a conventional, yet rarely used medical term that refers to the co-occurrence and pathophysiological interplay of type 2 diabetes mellitus (T2DM) and obesity. The escalating dual epidemics of these cardiometabolic conditions have made diabesity a major global health challenge, prompting research into ways to improve glycemic control and reduce excess adiposity.
Concurrently, a growing body of gut microbiome research points to the influence of these symbiotic microbes on host metabolic outcomes. Commensal bacteria ferment fiber into short-chain fatty acids (SCFAs), which stimulate glucagon-like peptide-1 (GLP-1) secretion. GLP-1 secretion, in turn, improves insulin sensitivity and promotes satiety, thereby altering host glycemic control.
Conversely, dysbiosis, which is defined as altered homeostasis in microbiome composition and function, has been linked to microbial products such as bacterial lipopolysaccharide (LPS) and hydrogen sulfide (H2S), which may promote inflammation or interfere with metabolic regulation, including GLP-1 signaling.
No previous trial has directly compared the therapeutic efficacy of metformin, the standard first-line pharmacological treatment for T2DM, with that of a microbiome-supporting high-fiber diet.
Trial compares fiber intervention with metformin monotherapy
This study aimed to address this knowledge gap and inform future diabesity interventions by using an 84-day, open-label, head-to-head trial to compare the therapeutic efficacy of metformin with that of a standardized high-fiber dietary intervention.
The study was conducted at Henan Provincial People's Hospital in China and included 48 adults aged 18 to 70 years with newly diagnosed T2DM. Only participants exhibiting a baseline glycated hemoglobin (HbA1c) between 6.5% and less than 9.0% with a concurrent body mass index (BMI) of at least 24 kg/m² were eligible.
A total of 46 participants completed the trial. Study participants first completed a two-week run-in period, after which they were randomized to either a high-fiber diet without medication (W group, n = 36) or metformin monotherapy (U group, n = 12). Two participants in the high-fiber group withdrew, leaving 34 at study completion.
The high-fiber diet incorporated formulas providing soluble and insoluble fibers, including inulin and resistant dextrin. Primary outcomes were participants' HbA1c and BMI at Day 84, with between-group comparisons adjusted for baseline values. Secondary outcomes included continuous glucose monitoring (CGM) metrics, meal tolerance tests (MTT), and dual-energy X-ray absorptiometry (DEXA).
Serial fecal samples (n = 184) underwent shotgun metagenomic analysis and metabolite quantification to monitor structural and functional changes in participants' gut microbiome over the study period.
Fiber improved blood sugar, weight, and gut microbial function
By Day 84, baseline-adjusted HbA1c was lower in the fiber group (6.3%) than in the metformin group (6.7%). The fiber group also had a lower baseline-adjusted mean BMI of 28.4 kg/m², compared with 30.2 kg/m² in the metformin group.
Participants in the dietary group also consumed less energy and lower amounts of several macronutrients during the intervention, which may have contributed to the differences in weight-related outcomes. Continuous glucose monitoring also showed lower glycemic variability in the fiber group, alongside lower whole-body fat mass and triglyceride concentrations at Day 84.
Metagenomics analyses revealed that fiber altered microbial community structure within 28 days, enriching bacteria including Bifidobacterium and Lactobacillus while depleting Bilophila wadsworthia, a bacterium linked to chronic inflammation. The metformin group showed no significant shift in overall microbial community structure during the 84-day trial, though smaller or more variable changes in particular microbes could not be ruled out.
Functional analyses found higher abundance of the acetate-production gene formate-tetrahydrofolate ligase (fhs) at Days 28 and 56, as well as a lower abundance of the H2S-production genes sarD and dsr at Day 84 in the fiber group. Fecal H2S concentrations were lower than in the metformin group at Days 28 and 56; however, these differences were no longer significant at Day 84.
Promising results, but larger trials are still needed
The present study found that an 84-day targeted high-fiber dietary intervention produced greater improvements in HbA1c and BMI than metformin in patients with newly diagnosed diabesity.
Importantly, this trial was conducted at a single center and included only 46 participants who completed treatment, with just 12 in the metformin group. Its short duration and unequal group sizes limit the certainty and broader applicability of the treatment comparison.
The study also did not measure GLP-1 levels; therefore, it could not directly test whether changes in SCFAs or H2S mediated the metabolic effects.
Baseline microbial features differed between participants who did and did not exhibit increased fecal acetate levels; however, these findings came from small exploratory subgroups. Larger independent studies are needed to determine whether these microbial features can reliably predict who is most likely to benefit from a high-fiber intervention.
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