Regional diets targeting gut microbial dynamics to support prolonged healthspan

In the last 150 years, we have seen a significant increase in average life expectancy, associated with a shift from infectious to non-communicable diseases. The rising incidence of these diseases, for which age is often the largest risk factor, highlights the need for contemporary societies to improve healthy ageing for their growing silver generations. As ageing is an inevitable, non-reversing and highly individualised process, we need to better understand how non-genetic factors like diet choices and commensal gut microbes can modulate the biology of ageing. In this review, we discuss how geographical and ethnic variations influence habitual dietary patterns, nutrient structure, and gut microbial profiles with potential impact on the human healthspan. Several gut microbial genera have been associated with healthy elderly populations but are highly variable across populations. It seems unlikely that a universal pro-longevity gut microbiome exists. Rather, the optimal microbiome appears to be conditional on the microbial functionality acting on regional- and ethnicity-specific trends driven by cultural food context. We also highlight dietary and microbial factors that have been observed to elicit individual and clustered biological responses. Finally, we identify next generation avenues to modify otherwise fixed host functions and the individual ageing trajectory by manipulating the malleable gut microbiome with regionally adapted, personalised food intervention regimens targeted at prolonging human healthspan

Development of multi-epitope peptide-based vaccines against SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic involving so far more than 15 million infections and 630,211 deaths. Effective vaccines are urgently needed to prevent SARS-CoV-2 infections. No vaccines have yet been approved for licensure by regulatory agencies. Even though host immune responses to SARS-CoV-2 infections are beginning to be unravelled, effective clearance of virus will depend on both humoral and cellular immunity. Additionally, the presence of Spike (S)-glycoprotein reactive CD4+ T-cells in the majority of convalescent patients is consistent with its significant role in stimulating B and CD8+ T-cells. The search for immunodominant epitopes relies on experimental evaluation of peptides representing the epitopes from overlapping peptide libraries which can be costly and labor-intensive. Recent advancements in B- and T-cell epitope predictions by bioinformatic analysis have led to epitope identifications. Assessing which peptide epitope can induce potent neutralizing antibodies and robust T-cell responses is a prerequisite for the selection of effective epitopes to be incorporated in peptide-based vaccines. This review discusses the roles of B- and T-cells in SARS-CoV-2 infections and experimental validations for the selection of B-, CD4+ and CD8+ T-cell epitopes which could lead to the construction of a multi-epitope peptide vaccine. Peptide-based vaccines are known for their low immunogenicity which could be overcome by incorporating immunostimulatory adjuvants and nanoparticles such as Poly Lactic-co-Glycolic Acid (PLGA) or chitosan

Safeguarding planetary health for Southeast Asia's future children

While we continue to deal with the ongoing COVID-19 pandemic, the past months have also revealed the sorry state of our collective planetary health, including in southeast Asia. Weeks after the 2021 UN climate change conference (known as COP26), Malaysia experienced intense flooding at a scale that has never been seen before,1 while the Philippines was once more hit by a super typhoon that killed hundreds and displaced a hundred thousand more.2 In the beginning of 2022, the Stockholm Resilience Centre announced that a fifth planetary boundary has already been breached—chemical pollution, particularly plastic—in addition to climate change, land use change, disrupted biogeochemical flows, and biodiversity loss.3 Southeast Asia is central source of plastic pollution, as most of the top five plastic-polluting countries are located in the region.4 Furthermore, as a biodiversity hotspot, the jungles of southeast Asia offer ideal conditions for another potential zoonotic outbreak, and it is vital to prevent future pandemics at the source.

Immunogenicity and safety of SARS-CoV-2 vaccines in clinical trials

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were first detected in Wuhan, China in December 2019 and resulted in a worldwide pandemic in 2020. SARS-CoV-2 infections totalled more than 180 million with 3.9 million deaths as of June 24, 2021. Tremendous research efforts have resulted in the development of at least 64 vaccine candidates that have reached Phase I to III clinical trials within 14 months. The primary efficacy endpoint for a random placebo-controlled clinical trial of a COVID-19 vaccine to be approved by US FDA should confer at least 50% protection against COVID-19. Three COVID-19 vaccines (BNT162b2, mRNA-1273 and Sputnik V) in clinical Phase III trials have now achieved >90% efficacy in preventing COVID-19. Since SARSCoV-2 is highly contagious, vaccines are expected to achieve at least 80% herd immunity in the world’s population to effectively prevent SARS-CoV-2 infections. An overview of safety, immunogenicity and efficacy of the current frontrunner vaccines are reviewed

Immunocytology of body cavity fluids: MOC-31, a monoclonal antibody discriminating between mesothelial and epithelial cells

This study was designed to assess whether monoclonal antibody MOC-31, which recognizes a membrane glycoprotein of 40-kd molecular weight present on epithelial cells and not on mesothelial cells, is a useful adjunct in the differential diagnosis of reactive pleural or ascitic fluids and adenocarcinoma. A panel of antibodies against carcinoembryonic antigen, epithelial membrane antigen, vimentin (antivimentin), keratin 18 (RGE-53), and cytokeratins of several molecular weights (AE1/AE3) was employed for comparison. Ninety-eight cases were selected based on the availability of pleural and peritoneal biopsy specimens for histologic confirmation. All cases with adenocarcinoma stained MOC-31 positive, including three cases that had not been identified by morphologic criteria. All cases of reactive mesothelial hyperplasia were negative, as well as five cases of malignant mesothelioma. One case of squamous cell carcinoma was also negative. Anti-carcinoembryonic antigen only identified half of the carcinoma cases, and anti-epithelial membrane antigen and both anticytokeratin antibodies were positive in the majority of tumor cells as well as in the mesothelial cells. This study indicates that monoclonal antibody MOC-31 is a highly sensitive and reliable reagent in the differential diagnosis between mesothelial and epithelial cells

Regional diets targeting gut microbial dynamics to support prolonged healthspan

In the last 150 years, we have seen a significant increase in average life expectancy, associated with a shift from infectious to non-communicable diseases. The rising incidence of these diseases, for which age is often the largest risk factor, highlights the need for contemporary societies to improve healthy ageing for their growing silver generations. As ageing is an inevitable, non-reversing and highly individualised process, we need to better understand how non-genetic factors like diet choices and commensal gut microbes can modulate the biology of ageing. In this review, we discuss how geographical and ethnic variations influence habitual dietary patterns, nutrient structure, and gut microbial profiles with potential impact on the human healthspan. Several gut microbial genera have been associated with healthy elderly populations but are highly variable across populations. It seems unlikely that a universal pro-longevity gut microbiome exists. Rather, the optimal microbiome appears to be conditional on the microbial functionality acting on regional- and ethnicity-specific trends driven by cultural food context. We also highlight dietary and microbial factors that have been observed to elicit individual and clustered biological responses. Finally, we identify next generation avenues to modify otherwise fixed host functions and the individual ageing trajectory by manipulating the malleable gut microbiome with regionally adapted, personalised food intervention regimens targeted at prolonging human healthspan.Nanyang Technological UniversityPublished versionDL received the support of Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, through the award of the Presidential Postdoctoral Fellowship (Grant No. 001991-00001)