Microbiota based personalized nutrition improves hyperglycaemia and hypertension parameters and reduces inflammation: a prospective, open label, controlled, randomized, comparative, proof of concept study.

Background: Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota through targeted nutrition can provide beneficial effects leading to the concept of personalized nutrition for health improvement. In this prospective clinical trial, we evaluated the impact of a microbiome-based targeted personalized diet on hyperglycaemic and hyperlipidaemic individuals. Specifically, BugSpeaks®-a microbiome profile test that profiles microbiota using next generation sequencing and provides personalized nutritional recommendation based on the individual microbiota profile was evaluated. Methods: A total of 30 participants with type 2 diabetes and hyperlipidaemia were recruited for this study. The microbiome profile of the 15 participants (test arm) was evaluated using whole genome shotgun metagenomics and personalized nutritional recommendations based on their microbiota profile were provided. The remaining 15 participants (control arm) were provided with diabetic nutritional guidance for 3 months. Clinical and anthropometric parameters such as HbA1c, systolic/diastolic pressure, c-reactive protein levels and microbiota composition were measured and compared during the study. Results: The test arm (microbiome-based nutrition) showed a statistically significant decrease in HbA1c level from 8.30 (95% confidence interval (CI), [7.74-8.85]) to 6.67 (95% CI [6.2-7.05]), p < 0.001 after 90 days. The test arm also showed a 5% decline in the systolic pressure whereas the control arm showed a 7% increase. Incidentally, a sub-cohort of the test arm of patients with >130 mm Hg systolic pressure showed a statistically significant decrease of systolic pressure by 14%. Interestingly, CRP level was also found to drop by 19.5%. Alpha diversity measures showed a significant increase in Shannon diversity measure (p < 0.05), after the microbiome-based personalized dietary intervention. The intervention led to a minimum two-fold (Log2 fold change increase in species like Phascolarctobacterium succinatutens, Bifidobacterium angulatum, and Levilactobacillus brevis which might have a beneficial role in the current context and a similar decrease in species like Alistipes finegoldii, and Sutterella faecalis which have been earlier shown to have some negative effects in the host. Overall, the study indicated a net positive impact of the microbiota based personalized dietary regime on the gut microbiome and correlated clinical parameters.

Study of amino acids absorption and gut microbiome on consumption of pea protein blended with enzymes-probiotics supplement.

The current randomized, double-blind, crossover clinical trial was conducted to evaluate changes in the amino acid absorption and gut microbiota on consumption of pea protein supplemented with an enzymes-probiotics blend (Pepzyme Pro). A total of 15 healthy subjects were instructed to take test (pea protein + Pepzyme Pro) or placebo (pea protein + maltodextrin) for 15 days with a 30-day washout period. Blood samples were analyzed for plasma-free amino acids, insulin, and C-reactive protein (CRP). Additionally, nitrogen levels in urine and feces, along with the composition of gut microbiota, were evaluated. On day 15, the test arm showed a tendency to increase the rate of absorption and total absorption (AUC) of amino acids compared with the placebo arm, though the increase was statistically insignificant. In addition, 15-day test supplementation showed a tendency to reduce Tmax of all the amino acids (statistically insignificant except alanine, p = 0.021 and glycine, p = 0.023) in comparison with the placebo supplementation. There were no changes in urine and fecal nitrogen levels as well as serum CRP levels in the test and placebo arm. The increase in serum insulin level after 4 h was statistically significant in both arms, whereas the insulin level of the placebo and test arm at 4 h was not statistically different. Supplementation showed changes with respect to Archaea and few uncharacterized species but did not show statistically significant variations in microbiome profile at the higher taxonomic levels. A study with large sample size and detailed gut microbiome analysis is warranted to confirm the results statistically as well as to characterize altered species. However, the current study could provide an inkling of a positive alteration in protein digestibility, amino acid absorption, and gut microbiome with regular consumption of protein and enzymes-probiotics blend. Clinical Trial Registration:clinicaltrials.gov/; identifier [CTRI/2021/10/037072].

Analysis of Microarray Data from Medulloblastoma Tissue Samples.

As a laboratory tool, microarray is used to detect the expression of thousands of genes at the same time. Typically, microscope slides have DNA microarrays that are printed with thousands of tiny spots in specified positions. Each spot contains a known DNA sequence or gene. These slides are commonly referred to as gene chips or DNA chips. The DNA molecules printed to each slide serve as probes to detect gene expression, which is also known as the transcriptome or the set of messenger RNA (mRNA) transcripts expressed by a group of genes. The goal of this chapter is to discuss the steps involved computational analysis of data after the completion of a typical microarray experiment.

Impending Mental Health Issues During Coronavirus Disease 2019 - Time for Personalized Nutrition Based on the Gut Microbiota to Tide Over the Crisis?

Coronavirus disease 2019 (COVID-19) is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our mental health as well. The uncertain future, fear of job loss, lockdown and negative news all around have taken a heavy toll on the mental health of individuals from across the world. Stress and anxiety can affect the COVID-19 patients even more. Recent study suggests COVID-19 infection may lead to post-traumatic stress disorder (PTSD). Certain prebiotics and probiotics have been shown to have anxiolytic effect through gut microbiota modulation. Incidentally, preliminary report also suggests a differential microbial profile in COVID-19 patients as compared to healthy individuals. Gut microbiota's role in anxiety and depression is well studied. The importance of the "gut-brain" axis has been implicated in overall mental health. It is known that diet, environmental factors and genetics play an important role in shaping gut microbiota. Trials may be initiated to study if personalized diet and supplementation based on individual's gut microbiome profile may improve the general mental well-being of people prone to anxiety during this pandemic. Also, COVID-19 patients may be provided personalized nutritional therapy based on their gut microbiota profile to see if PTSD and anxiety symptoms can be alleviated.

Gut microbiota and Covid-19- possible link and implications.

Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. Role of the gut microbiota in influencing lung diseases has been well articulated. It is also known that respiratory virus infection causes perturbations in the gut microbiota. Diet, environmental factors and genetics play an important role in shaping gut microbiota which can influence immunity. Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies.

Role of polypyrimidine tract binding protein in mediating internal initiation of translation of interferon regulatory factor 2 RNA.

BACKGROUND: Earlier we have reported translational control of interferon regulatory factor 2 (IRF2) by internal initiation (Dhar et al, Nucleic Acids Res, 2007). The results implied possible role of IRF2 in controlling the intricate balance of cellular gene expression under stress conditions in general. Here we have investigated the secondary structure of the Internal Ribosome Entry Site of IRF2 RNA and demonstrated the role of PTB protein in ribosome assembly to facilitate internal initiation. METHODOLOGY/PRINCIPAL FINDINGS: We have probed the putative secondary structure of the IRF2 5'UTR RNA using various enzymatic and chemical modification agents to constrain the secondary structure predicted from RNA folding algorithm Mfold. The IRES activity was found to be influenced by the interaction of trans-acting factor, polypyrimidine tract binding protein (PTB). Deletion of 25 nts from the 3'terminus of the 5'untranslated region resulted in reduced binding with PTB protein and also showed significant decrease in IRES activity compared to the wild type. We have also demonstrated putative contact points of PTB on the IRF2-5'UTR using primer extension inhibition assay. Majority of the PTB toe-prints were found to be restricted to the 3'end of the IRES. Additionally, Circular Dichroism (CD) spectra analysis suggested change in the conformation of the RNA upon PTB binding. Further, binding studies using S10 extract from HeLa cells, partially silenced for PTB gene expression, resulted in reduced binding by other trans-acting factors. Finally, we have demonstrated that addition of recombinant PTB enhances ribosome assembly on IRF2 IRES suggesting possible role of PTB in mediating internal initiation of translation of IRF2 RNA. CONCLUSION/SIGNIFICANCE: It appears that PTB binding to multiple sites within IRF2 5'UTR leads to a conformational change in the RNA that facilitate binding of other trans-acting factors to mediate internal initiation of translation.

Translational control of the interferon regulatory factor 2 mRNA by IRES element.

Translational control represents an important mode of regulation of gene expression under stress conditions. We have studied the translation of interferon regulatory factor 2 (IRF2) mRNA, a negative regulator of transcription of interferon-stimulated genes and demonstrated the presence of internal ribosome entry site (IRES) element in the 5'UTR of IRF2 RNA. Various control experiments ruled out the contribution of leaky scanning, cryptic promoter activity or RNA splicing in the internal initiation of IRF2 RNA. It seems IRF2-IRES function is not sensitive to eIF4G cleavage, since its activity was only marginally affected in presence of Coxsackievirus 2A protease. Interferon alpha treatment did not affect the IRF2-IRES activity or the protein level significantly. Also, in cells treated with tunicamycin [an agent causing endoplasmic reticulum (ER) stress], the IRF2-IRES activity and the protein levels were unaffected, although the cap-dependent translation was severely impaired. Analysis of the cellular protein binding with the IRF2-IRES suggests certain cellular factors, which might influence its function under stress conditions. Interestingly, partial knockdown of PTB protein significantly inhibited the IRF2-IRES function. Taken together, it appears that IRF2 gene expression during stress condition is controlled by the IRES element, which in turn influences the cellular response.