Effects of Microbiota-Driven Therapy on Circulating Trimethylamine-N-Oxide Metabolism: A Systematic Review and Meta-Analysis

Aim: This study was designed to systematically evaluate the effects of microbiota-driven therapy on decreasing TMAO and its related metabolites.Methods and Results: PubMed, EMBASE and Cochrane Library databases were searched (up to July 2021). Randomized controlled trials (RCTs), compared microbiota-driven therapy (prebiotics, probiotics, or synbiotics) with placebo on decreasing TMAO and its related metabolites, were eligible. Two researchers extracted the data independently and the disagreement was resolved by a third researcher. The risk of bias of included study was evaluated using Cochrane tool (RoB 2.0). Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 12.0 software. Ten studies (12 arms) involving 342 patients (168 patients in the intervention group and 174 patients in the control group) were included. Compared with the control group, microbiota-driven therapy did not reduce circulating TMAO [SMD = −0.05, 95% CI (−0.36, 0.26), P = 0.749], choline [SMD = −0.34, 95% CI (−1.09, 0.41), P = 0.373], betaine aldehyde [SMD = −0.704, 95% CI (−1.789, 0.382), P = 0.204], and L-carnatine [SMD = −0.06, 95% CI (−0.38, 0.25), P = 0.692].Conclusion: Current evidence does not support that microbiota-driven treatment reduce circulating levels of TMAO, choline, betaine aldehyde, and L-carnitine. However, given the small sample size, this conclusion needs to be proved in the future.Systematic Review Registration: PROSPERO:CRD42019119107.

Fragrance in Pandanus amaryllifoliusRoxb. Despite the Presence of a Betaine Aldehyde Dehydrogenase 2

Pandanus amaryllifoliusRoxb. accumulates the highest concentration of the major basmati aroma volatile 2-acetyl-1-pyrroline (2AP) in the plant kingdom. The expression of 2AP is correlated with the presence of a nonfunctional betaine aldehyde dehydrogenase 2(BADH2) in aromatic rice and other plant species. In the present study, a full-length BADH2 sequence was reconstructed from the transcriptome data of leaf tissue from P. amaryllifolius seedlings. Based on this sequence, a 1509 bp coding sequence was defined that encoded a 54 kD PaBADH2protein. This revealed the presence of a full-length BADH2 protein in P. amaryllifolius. Moreover, quantitative real-time PCR analysis, combined with BADH2 enzyme activity, confirmed the expression and functionality of the PaBADH2 protein. To understand the apparent structural variation, docking analysis was carried out in which protein showed a good affinity with both betaine aldehyde (BAD) and γ-aminobutyraldehyde (GAB-ald) as substrates. Overall, the analysis showed the presence of a functional BADH2, along with substantial 2AP synthesis (4.38 ppm). Therefore, we conclude that unlike all other plants studied to date, 2AP biosynthesis in P. amaryllifolius is not due to the inactivation of BADH2.

Betaine Aldehyde Dehydrogenase (BADH) vs. Flavodoxin (Fld): Two Important Genes for Enhancing Plants Stress Tolerance and Productivity

Abiotic stresses, mainly salinity and drought, are the most important environmental threats that constrain worldwide food security by hampering plant growth and productivity. Plants cope with the adverse effects of these stresses by implementing a series of morpho-physio-biochemical adaptation mechanisms. Accumulating effective osmo-protectants, such as proline and glycine betaine (GB), is one of the important plant stress tolerance strategies. These osmolytes can trigger plant stress tolerance mechanisms, which include stress signal transduction, activating resistance genes, increasing levels of enzymatic and non-enzymatic antioxidants, protecting cell osmotic pressure, enhancing cell membrane integrity, as well as protecting their photosynthetic apparatus, especially the photosystem II (PSII) complex. Genetic engineering, as one of the most important plant biotechnology methods, helps to expedite the development of stress-tolerant plants by introducing the key tolerance genes involved in the biosynthetic pathways of osmolytes into plants. Betaine aldehyde dehydrogenase (BADH) is one of the important genes involved in the biosynthetic pathway of GB, and its introduction has led to an increased tolerance to a variety of abiotic stresses in different plant species. Replacing down-regulated ferredoxin at the acceptor side of photosystem I (PSI) with its isofunctional counterpart electron carrier (flavodoxin) is another applicable strategy to strengthen the photosynthetic apparatus of plants under stressful conditions. Heterologous expression of microbially-sourced flavodoxin (Fld) in higher plants compensates for the deficiency of ferredoxin expression and enhances their stress tolerance. BADH and Fld are multifunctional transgenes that increase the stress tolerance of different plant species and maintain their production under stressful situations by protecting and enhancing their photosynthetic apparatus. In addition to increasing stress tolerance, both BADH and Fld genes can improve the productivity, symbiotic performance, and longevity of plants. Because of the multigenic and complex nature of abiotic stresses, the concomitant delivery of BADH and Fld transgenes can lead to more satisfying results in desired plants, as these two genes enhance plant stress tolerance through different mechanisms, and their cumulative effect can be much more beneficial than their individual ones. The importance of BADH and Fld genes in enhancing plant productivity under stress conditions has been discussed in detail in the present review.