Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes

Abstract

The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced the risk of a variety of complications, such as diabetes and cardiovascular diseases. In the present review, we have highlighted the new insights on the complex relationships between diet-induced modulation of gut microbiota and metabolic disorders, including diabetes. Literature from various library databases and electronic searches (ScienceDirect, PubMed, and Google Scholar) were randomly collected. There exists a complex relationship between diet and gut microbiota, which alters the energy balance, health impacts, and autoimmunity, further causes inflammation and metabolic dysfunction, including diabetes. Faecalibacterium prausnitzii is a butyrate-producing bacterium, which plays a vital role in diabetes. Transplantation of F. prausnitzii has been used as an intervention strategy to treat dysbiosis of the gut's microbial community that is linked to the inflammation, which precedes autoimmune disease and diabetes. The review focuses on literature that highlights the benefits of the microbiota especially, the abundant of F. prausnitzii in protecting the gut microbiota pattern and its therapeutic potential against inflammation and diabetes.

Keywords: Faecalibacterium prausnitzii; diabetes; diet; gut microbiota; novel strategies.

Figure 1

Healthy gut microbiota versus the altered microbiota. Based on Patterson et al [34], healthy gut microbiota composed of predominant phyla Firmicutes (60%) to Bacteroidetes, which restricts lipopolysaccharide (LPS) translocation by the integrity of the intestinal epithelial barrier and harvest energy for the host. Unhealthy microbiota profile causes metabolic dysfunction in peripheral organs, leading to increased adiposity, chronic inflammation, oxidative stress, diabetes, and obesity. In addition, the secretion of gut hormones (incretins ghrelin, amylin) can affect metabolic syndrome and diabetes [19,34,35]. IEC, intestinal epithelial cell; GLP-1, glucagon-like peptide-1; GIP, gastric inhibitory peptide; SCFA, short chain fatty acid.

Figure 2

Dietary patterns, diet composition, and probiotics determine colonic microbiota composition and functions.

Figure 3

Dietary fiber is a source of complex carbohydrates, which are required for the production of SCFA. When the diversity of the microbiota is high, the accessible rate of complex carbohydrates is relatively high. The production of multiple types of SCFA helps not only energy source for a host and microbiota, but also to recruit additional diversity to the gut microbiota. SCFA is also a substrate for gluconeogenesis, which modulates central metabolism, and are involved in signaling to the host by activating G-protein-coupled receptors, such as GPR41 and GPR43, which triggers the release of the hormone GLP1secretion, increasing insulin sensitivity, and inducing satiety [141]. On the other hand, GPR41 activate peptide YY (PYY), an intestinal hormone that influences gut motility, enhances intestinal transit rate, and decreases energy harvest from the diet [139]. Butyrate can elevate the regulatory T cells (Tregs), thus suppress chronic inflammation.

Figure 4

Altered microbial communities enhance the gut permeability and cause leaky gut. The lipopolysaccharide binding protein (LBP), synthesized from the liver, acts as a carrier of LPS. LPS is the primary constituents of the outer membrane of intestinal bacteria, known to cause chronic inflammation in the host. LPS/LPB complex assembles with membrane-bound CD14 (cluster of differentiation 14) molecules and toll-like receptor 4 (TLR4) on the surface of macrophages in the host. TLR4signaling is initiated by ligand-induced dimerization of receptors, which engage with adaptor proteins like MYD88 (myeloid differentiation primary response protein 88) and MAL (MYD88-adaptor-like protein). These downstream signaling pathways stimulate the connections among IL-1R-associated kinases (IRAKs) and the adaptor molecules TNF receptor-associated factors (TRAF). The association of these molecules triggers the mitogen-activated protein kinases (MAPK), JUN N-terminal kinase (JNK) and p38, and subsequently activate the transcription factors, such as nuclear factor-κB (NF-κB), interferon regulatory factors (IRF), cyclic AMP-responsive element-binding protein (CREB) and activator protein 1 (AP1) [168,169]. TLR4 signaling downstream pathways induce pro-inflammatory cytokines that impair insulin secretion and insulin mRNA expression in human beta cell islets [175]. NF-κB could also inhibit insulin gene expression by interacting with CREB [160].

Figure 5

Novel strategies for diabetes prevention by dietary intervention and a transplant of F. prausnitzii to the diabetic individual—Isolation of F. prausnitzii is either from experimental animals or healthy individual and introduce into diabetic persons through the infusion of the stool or by mouth in the form of a capsule. The initiation step for the identification of a strategy to adapt the gut flora is through components of the diet interventions. Appropriate experimental studies (in vitro, placebo or animal models) and elements in independent cohorts are used to explain the principal mechanisms and to pilot curative approaches to modulating the intestinal bacteria, which laid the foundations for probiotics or prebiotics trials in humans to improve diabetes and its complications.