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. 2024 Jun 27;12(3):e003964.
doi: 10.1136/bmjdrc-2023-003964.

Unveiling contrasts in microbiota response: A1c control improves dysbiosis in low-A1c T2DM, but fails in high-A1c cases-a key to metabolic memory?

Thiago Fraga Napoli  1   2 , Ramon V Cortez  3 , Luiz Gustavo Sparvoli  3 , Carla R Taddei  3 , Joao Eduardo Nunes Salles  2
Affiliations

Unveiling contrasts in microbiota response: A1c control improves dysbiosis in low-A1c T2DM, but fails in high-A1c cases-a key to metabolic memory?

Thiago Fraga Napoli et al. BMJ Open Diabetes Res Care. .

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) is associated with dysbiosis in the gut microbiota (MB). Individually, each medication appears to partially correct this. However, there are no studies on the response of the MB to changes in A1c. Therefore, we investigated the MB's response to intensive glycemic control.

Research design and methods: We studied two groups of patients with uncontrolled T2DM, one group with an A1c <9% (18 patients-G1) and another group with an A1c >9% (13 patients-G2), aiming for at least a 1% reduction in A1c. We collected A1c and fecal samples at baseline, 6, and 12 months. G1 achieved an average A1c reduction of 1.1%, while G2 a reduction of 3.13%.

Results: G1's microbiota saw a decrease in Erysipelotrichaceae_UCG_003 and in Mollicutes order (both linked to metabolic syndrome and associated comorbidities). G2, despite having a more significant reduction in A1c, experienced an increase in the proinflammatory bacteria Megasphaera and Acidaminococcus, and only one beneficial genus, Phascolarctobacterium, increased, producer of butyrate.

Conclusion: Despite a notable A1c outcome, G2 could not restore its MB. This seeming resistance to change, leading to a persistent inflammation component found in G2, might be part of the "metabolic memory" in T2DM.

Keywords: diabetes mellitus, type 2; metabolism.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Longitudinal A1c evolution. Groups showed significant change until 6 months, reaching the same A1c value (p>0.05) and remained stable until 12 months.
Figure 2
Figure 2
Principal Coordinates Analysis (PCoA) (A) Baseline beta diversity G1 vs G2. (B) Beta diversity at 6 months, according to A1c variation (< 1%, 1–1.9%, > 2%). (C) Beta diversity at 12 months, according to A1c. All analyses (A–C) were non-significant.
Figure 3
Figure 3
Main bacterial genera at baseline, 6 and 12 months. *Significantly different 0–6 m (at 6 months) and 6–12 or 0–12 months (12 months). See figure 4 for specific data.
Figure 4
Figure 4
Intragroup genera variation. An asterisk denotes statistical significance.
See this image and copyright information in PMC

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