Introduction:
The gut microbiota is a complex ecosystem containing groups of bacteria of different species. The gut microbiota mainly contains bacteria, and others present are fungi, viruses, archaea, and protists. Diabetes is increasing exponentially around the world. Type-2 diabetes may emerge due to changes in the gut microbiota.
What Is the Gut Microbiota?
The human body contains trillions of bacteria. The genetic content of the microbiota is 150 times that of other body parts. The gut microbiota includes bacteria, viruses, fungi, archaea, etc. Studies have found that gut microbiota is a part of the onset of obesity and is responsible for the energy-harvesting process in the development of obesity.
Type 2 diabetes is a metabolic disease caused by decreased insulin secretion by the beta cells of the pancreas, leading to increased blood glucose levels.
The Role of Gut Microbiota in the Pathogenesis of Type 2 Diabetes:
Studies have found that the gut microbiota plays a role in the development of immunity. Type-2 diabetes is thought to be caused by obesity and is related to abnormal energy metabolism and low-level chronic inflammation of the fat tissues. Some studies have found a link between type 2 diabetes and the gut microbiota.
Gut microbiota has been associated with the progression of prediabetes, like insulin resistance. This condition is linked to an altered gut microbiota, showing an elevation in the ratio of Firmicutes/Bacteroidetes compared to healthy people.
A study showed that there was a change in the energy harvest of the hosts when the transplantation of gut microbiota was done among obese animals. Altered gut microbiota causes changes in the permeability of the intestine and increases the secretion of metabolic endotoxins. This, in turn, led to chronic low-level inflammation, the pathogenesis of insulin resistance, and type 2 diabetes onset.
A recent study has shown that bacterial species like Bacteroidetes thetaiotaomicron, Akkermansia muciniphilia, and Escherichia coli influence intestinal mucus and the glycocalyx layer, affecting intestinal permeability. Apart from gut microbiota changes, there may be changes in the endocannabinoid system and alkaline phosphatase activity. These changes also influence intestinal permeability and the pathogenesis of insulin resistance.
Alteration of Firmicutes/Bacteroidetes may change the host's energy metabolism through a mechanism involving polysaccharide utilization loci. The accumulation of gut-derived bacterial inflammatory molecules like peptidoglycans and flagellin accelerates type-2 diabetes.
Probiotic strains are considered to maintain glucose levels in the blood and hence play a role in improving type 2 diabetes. Probiotics help modulate the immune system. Therefore, probiotics help with obesity-induced low-level chronic inflammation during the onset and progression of type 2 diabetes. According to a study, probiotics help in the reduction of inflammatory IFN-ˠ and IL-2 or IL-10 production. It also helps increase the production of IL-10 in diabetic animals.
Another study conducted on rats has shown that Lactobacillus reuteri GMNL-263 helps suppress serum glucose, insulin, leptin, C-peptide, glycated hemoglobin, GLP-1 level, inflammatory IL-6, TNF in adipose tissues, PPAR-ˠ, and GLUT4 gene expression.
Probiotic strains help reduce chronic inflammation through their antioxidant effects.
These probiotics help reduce oxidative stress in the pancreas and thereby reduce the effects of oxidative stress on the beta cells of the pancreas.
When probiotics are given as a supplement, they affect lipid metabolism and change total serum cholesterol levels and LDL cholesterol. These changes help reduce the risk of type-2 diabetes. Studies have found that probiotic strains can suppress endotoxemia, a triggering factor for insulin resistance.
A probiotic strain called L. casei Zhang affects osteoclastin. This strain tends to increase osteoclastin levels and thereby improve oral glucose tolerance.
How Are the Complications of Type-2 Diabetes Related to Microbiota?
Microbiota and type-2 diabetes are linked, so their complications are also related.
Diabetic Retinopathy:
Gram-positive bacteria and Coagulase-negative staphylococci are frequently found among diabetic patients, especially those with retinopathy. Another study found staphylococcus epidermidis and staphylococcus aureus in the conjunctiva of type 2 diabetics.
Parkinson’s disease is a complication of chronic diabetic neuropathy. Hence, the conjunctiva of Parkinson’s disease shows more staphylococcus.
Renal Toxicity and Kidney Stones:
Individuals with type-2 diabetes suffer from kidney toxicity. This may include kidney stones. People with kidney disease show changes in 190 microbial operational taxonomic units ( OTUs). The most commonly found are Enterobacteriaceae among people with kidney disease.
Oxalobacter formigenes, a gut microbe, help improve kidney stone conditions.
Hypertension:
Hypertension is related to type-2 diabetes. It is a risk factor for cardiovascular disease. A symptom of metabolic syndrome. The gut microbiota partially regulates the metabolic syndrome. The gut microbiota produces one of the end products called propionate. This pend product increases renal olfactory receptor 78 (Olfr 78). This helps mediate the secretion of renin. This renin helps regulate blood pressure.
Another study has revealed that Lactobacillus johnsonii La 1 maintained blood glucose levels and prevented increased blood pressure by reducing renal sympathetic nerve activity and increasing parasympathetic nerve activity through the sympathoadrenal axis.
Atherosclerosis:
Individuals with type 2 diabetes generally have increased lipids in their serum. This may lead to atherosclerosis. It was found that veillanella and Streptococcus correlated with atherosclerosis. The plasma cholesterol was correlated with Streptococcus, Neisseria, and Fusobacterium. Probiotics increase the speed of the conversion of cholesterol into primary bile. This helps reduce serum lipids.
Cystic Fibrosis:
In cystic fibrosis, microbes in the affected lung, gut microbiota, and diet are responsible for cystic fibrosis in type 2 diabetes. Probiotics help treat the symptoms caused by cystic fibrosis. A study showed that Lactobacillus GG helped reduce intestinal inflammation and pulmonary exacerbation rates among individuals with cystic fibrosis.
Diabetic Foot Ulcers:
Staphylococcus species, P. auregenosa, and E. coli were found among people with diabetic foot ulcers.
Alzheimer’s Disease:
A study has found a link between insulin deficiency and Alzheimer’s disease. Enteria bacteria were considered for preventing and treating Alzheimer’s disease. A probiotic strain called L. rhamnosus JB-1 is deemed an effective modulator of GABA receptors lost in Alzheimer’s disease.
Conclusion:
Recent studies have found that type-2 diabetes influences the gut microbiota. The microbiota plays a role in the onset of type 2 diabetes and its complications. Hence, it becomes important to know about the gut microbiota, their pathogenesis in type 2 diabetes, and their role in the complications of type-2 diabetes. Knowing helps identify the problem early and helps seek help from healthcare providers. Early diagnosis helps in getting effective treatment. This, in turn, helps in achieving a good quality of life.
