Modulation of gut microbiota dysbioses in type 2 diabetic patients by macrobiotic Ma-Pi 2 diet

Abstract

The gut microbiota exerts a role in type 2 diabetes (T2D), and deviations from a mutualistic ecosystem layout are considered a key environmental factor contributing to the disease. Thus, the possibility of improving metabolic control in T2D by correcting gut microbiome dysbioses through diet has been evaluated. Here, we explore the potential of two different energy-restricted dietary approaches – the fibre-rich macrobiotic Ma-Pi 2 diet or a control diet recommended by Italian professional societies for T2D treatment – to correct gut microbiota dysbioses in T2D patients. In a previous 21-d open-label MADIAB trial, fifty-six overweight T2D patients were randomised to the Ma-Pi 2 or the control diet. For the present study, stools were collected before and after intervention from a subset of forty MADIAB participants, allowing us to characterise the gut microbiota by 16S rRNA sequencing and imputed metagenomics. To highlight microbiota dysbioses in T2D, the gut microbiota of thirteen normal-weight healthy controls were characterised. According to our findings, both diets were effective in modulating gut microbiome dysbioses in T2D, resulting in an increase of the ecosystem diversity and supporting the recovery of a balanced community of health-promoting SCFA producers, such as Faecalibacterium, Roseburia, Lachnospira, Bacteroides and Akkermansia. The Ma-Pi 2 diet, but not the control diet, was also effective in counteracting the increase of possible pro-inflammatory groups, such as Collinsella and Streptococcus, in the gut ecosystem, showing the potential to reverse pro-inflammatory dysbioses in T2D, and possibly explaining the greater efficacy in improving the metabolic control.

Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes

“…Six studies recruited only individuals diagnosed with type 2 diabetes mellitus [29, 30, 32–35]. One study compared participants with type 2 diabetes mellitus and control participants at baseline, prior to the introduction of any intervention, however, these 13 participants were not included in the analyses reported here [32]. Two studies [31, 36] reported on a sample including individuals with and without type 2 diabetes mellitus (Table 1).…”

“…Five studies reported treatment regimens: insulin injection ( n  = 11), insulin secretagogue ( n  = 34), metformin ( n  = 52), sulfonylurea ( n  = 12), α-glucosidase inhibitor ( n  = 41), sitagliptin ( n  = 7), thiazolidinedione ( n  = 1), peroxisome proliferator-activated receptor γ (PPAR-γ) antagonist ( n  = 15) or statins ( n  = 5) [30, 31, 34]. One study recruited individuals who managed their type 2 diabetes mellitus through diet only [29], and two studies used eligibility criteria that restricted the use of insulin but allowed hypoglycaemic drugs and dietary interventions, but provided no specific details [32, 33]. Two studies [35, 36] did not report any treatment regimens (Table 1).…”

“…All included studies involved some form of dietary intervention, including dietary manipulation and/or supplements. One RCT supplemented participants with a synbiotic [35], one single-group study instructed participants to follow a strict vegetarian diet [36], one RCT [32] instructed participants to follow a strict Ma-Pi diet [37] and a further RCT asked participants to follow a diet recommended for type 2 diabetes mellitus incorporating an increased intake of sardines [29]. The last two of these studies included information on nutrient intake, although Balfegó et al [29] did not provide any information on what constituted the type 2 diabetic diet.…”

“…Seven studies provided detail on outcome assessors [29–34, 36] and five studies provided sufficient detail to establish the likely absence of selective outcome reporting [29, 32–35]. Overall, seven of the studies were considered to be low risk of bias [29–34, 36] and the risk of bias of one [35] was unclear (Table 2).…”

“…Two studies comparing supplementation with a prebiotic vs control for 12 weeks [34] and the Ma-Pi diet vs a control diet for 21 days [32] provided sufficient data for meta-analyses to be conducted. Changes in the relative abundance of bacteria in the genera Bifidobacterium (SMD 1.29% [95% CI −4.45, 7.03], I 2  = 33%), Roseburia (SMD −0.85% [95% CI −2.91, 1.21], I 2  = 79%) and Lactobacillus (SMD 0.04% [95% CI −0.01, 0.09], I 2  = 0%) (ESM Fig.…”