*Review* **The Effects of Almonds on Gut Microbiota, Glycometabolism, and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials**

**Omorogieva Ojo 1,\*, Xiao-Hua Wang 2, Osarhumwese Osaretin Ojo <sup>3</sup> and Amanda Rodrigues Amorim Adegboye <sup>4</sup>**


**Citation:** Ojo, O.; Wang, X.-H.; Ojo, O.O.; Adegboye, A.R.A. The Effects of Almonds on Gut Microbiota, Glycometabolism, and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. *Nutrients* **2021**, *13*, 3377. https://doi.org/ 10.3390/nu13103377

Academic Editor: Roberto Cangemi

Received: 1 September 2021 Accepted: 23 September 2021 Published: 26 September 2021

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**Abstract:** The use of nutritional interventions for managing diabetes is one of the effective strategies aimed at reducing the global prevalence of the condition, which is on the rise. Almonds are the most consumed tree nut and they are known to be rich sources of protein, monounsaturated fatty acids, essential minerals, and dietary fibre. Therefore, the aim of this review was to evaluate the effects of almonds on gut microbiota, glycometabolism, and inflammatory parameters in patients with type 2 diabetes. Methods: This systematic review and meta-analysis was carried out according to the preferred reporting items for systematic review and meta-analysis (PRISMA). EBSCOhost, which encompasses the Health Sciences Research Databases; Google Scholar; EMBASE; and the reference lists of articles were searched based on population, intervention, control, outcome, and study (PICOS) framework. Searches were carried out from database inception until 1 August 2021 based on medical subject headings (MesH) and synonyms. The meta-analysis was carried out with the Review Manager (RevMan) 5.3 software. Results: Nine randomised studies were included in the systematic review and eight were used for the meta-analysis. The results would suggest that almond-based diets have significant effects in promoting the growth of short-chain fatty acid (SCFA) producing gut microbiota. Furthermore, the meta-analysis showed that almond-based diets were effective in significantly lowering (*p* < 0.05) glycated haemoglobin (HbA1c) levels and body mass index (BMI) in patients with type 2 diabetes. However, it was also found that the effects of almonds were not significant (*p* > 0.05) in relation to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and Tumour necrosis factor α, TNF-α), glucagon-like peptide-1 (GLP-1), homeostatic model assessment of insulin resistance (HOMA–IR), and fasting insulin. The biological mechanisms responsible for the outcomes observed in this review in relation to reduction in HbA1c and BMI may be based on the nutrient composition of almonds and the biological effects, including the high fibre content and the low glycaemic index profile. Conclusion: The findings of this systematic review and meta-analysis have shown that almond-based diets may be effective in promoting short-chain fatty acid-producing bacteria and lowering glycated haemoglobin and body mass index in patients with type 2 diabetes compared with control. However, the effects of almonds were not significant (*p* > 0.05) with respect to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and TNF-α), GLP-1, HOMA–IR, and fasting insulin.

**Keywords:** type 2 diabetes; almonds; tree nuts; glycated haemoglobin; gut microbiota; body mass index

### **1. Introduction**

The use of nutritional interventions is one of the strategies for managing diabetes, which is on the increase worldwide. It is projected that the global prevalence of diabetes could reach 700 million by 2045, up by 51% from 463 million who were living with the condition in 2019 [1]. Over 90% of people with diabetes have type 2 diabetes, which is linked to lifestyle factors [2], and this has implications in terms of morbidity and mortality. Poor diabetes control increases the costs of healthcare as a result of potentially avoidable hospital treatment and drug prescription and in the UK, the total annual spending on patients with type 2 diabetes is expected to rise to about £2.2 billion by 2040–2050 [3,4]. Therefore, nutritional interventions, which are effective in terms of clinical outcomes, are often recommended for diabetes management [5]. In this regard, the use of nuts, including tree nuts, such as almond, walnut, hazelnut, cashew nuts and Brazil nuts, and groundnuts (mainly peanuts), which are high in unsaturated fatty acids and are rich sources of bioactive nutrients that have significant metabolic and cardiovascular health benefits, have been suggested [6,7].

Almonds are the most consumed tree nut and they are known to be rich sources of protein, monounsaturated fatty acids, essential minerals, and dietary fibre [6,8]. The role of dietary fibre in modulating gut microbiota dysbiosis and in the regulation of glycaemic parameters have been demonstrated in previous systematic reviews and metaanalyses [9,10] and in randomised controlled trials [11,12].

#### *1.1. Description of the Intervention*

Nuts have been part of the human diet for centuries. Nuts are included in different recipes and, more recently, nuts, particularly almonds, have been consumed as a healthy snack [13]. However, the level of consumption of nuts may vary globally, across different populations. Almonds are tree nuts that have a low glycaemic index, are rich in dietary fibre and unsaturated fatty acids, and have low carbohydrate content [6]. The macro- and micronutrient components of almonds, including monounsaturated fatty acids, polyunsaturated fatty acids, fibre, vitamins, minerals, phytosterols, and polyphenols, have been associated with health benefits including anti-inflammatory and lipid-lowering properties [6,8]. Almonds also have antioxidant properties [8]. The polyphenols and fibre content of almonds may be used as substrates for gut microbial growth and regulation of gut microbiota [8]. It has been suggested that there is an inverse relationship between the consumption of nuts and the risk of developing type 2 diabetes [6].
