Bacterial membrane vesicles in the pathogenesis and treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and debilitating condition of relapsing and remitting inflammation in the gastrointestinal tract. Conventional therapeutic approaches for IBD have shown limited efficacy and detrimental side effects, leading to the quest for novel and effective treatment options for the disease. Bacterial membrane vesicles (MVs) are nanosized lipid particles secreted by lysis or blebbing processes from both Gram-negative and Gram-positive bacteria. These vesicles, known to carry bioactive components, are facsimiles of the parent bacterium and have been implicated in the onset and progression, as well as in the amelioration of IBD. This review discusses the overview of MVs and their impact in the pathogenesis, diagnosis, and treatment of IBD. We further discuss the technical challenges facing this research area and possible research questions addressing these challenges. We summarize recent advances in the diverse relationship between IBD and MVs, and the application of this knowledge as a viable and potent therapeutic strategy for IBD.

Microbial ecology and evolution is key to pandemics: using the coronavirus model to mitigate future public health challenges.

Pandemics are global challenges that lead to total disruption of human activities. From the inception of human existence, all pandemics have resulted in loss of human lives. The coronavirus disease caused by SAR-CoV-2 began in China and is now at the global scale with an increase in mortality and morbidity. Numerous anthropogenic activities have been implicated in the emergence and severity of pandemics, including COVID-19. These activities cause changes in microbial ecology, leading to evolution due to mutation and recombination. This review hypothesized that an understanding of these anthropogenic activities would explain the dynamics of pandemics. The recent coronavirus model was used to study issues leading to microbial evolution, towards preventing future pandemics. Our review highlighted anthropogenic activities, including deforestation, mining activities, waste treatment, burning of fossil fuel, as well as international travels as drivers of microbial evolution leading to pandemics. Furthermore, human-animal interaction has also been implicated in pandemic incidents. Our study recommends substantial control of such anthropogenic activities as having been highlighted as ways to reduce the frequency of mutation, reduce pathogenic reservoirs, and the emergence of infectious diseases.

The deuce-ace of Lassa Fever, Ebola virus disease and COVID-19 simultaneous infections and epidemics in West Africa: clinical and public health implications.

Globally, the prevailing COVID-19 pandemic has caused unprecedented clinical and public health concerns with increasing morbidity and mortality. Unfortunately, the burden of COVID-19 in Africa has been further exacerbated by the simultaneous epidemics of Ebola virus disease (EVD) and Lassa Fever (LF) which has created a huge burden on African healthcare systems. As Africa struggles to contain the spread of the second (and third) waves of the COVID-19 pandemic, the number of reported cases of LF is also increasing, and recently, new outbreaks of EVD. Before the pandemic, many of Africa's frail healthcare systems were already overburdened due to resource limitations in staffing and infrastructure, and also, multiple endemic tropical diseases. However, the shared epidemiological and pathophysiological features of COVID-19, EVD and LF as well their simultaneous occurrence in Africa may result in misdiagnosis at the onset of infection, an increased possibility of co-infection, and rapid and silent community spread of the virus(es). Other challenges include high population mobility across porous borders, risk of human-to-animal transmission and reverse zoonotic spread, and other public health concerns. This review highlights some major clinical and public health challenges toward responses to the COVID-19 pandemic amidst the deuce-ace of recurrent LF and EVD epidemics in Africa. Applying the One Health approach in infectious disease surveillance and preparedness is essential in mitigating emerging and re-emerging (co-)epidemics in Africa and beyond.

Faecal microbial biomarkers in early diagnosis of colorectal cancer.

Colorectal cancer (CRC) is ranked as the second most common cause of cancer deaths and the third most common cancer globally. It has been described as a 'silent disease' which is often easily treatable if detected early-before progression to carcinoma. Colonoscopy, which is the gold standard for diagnosis is not only expensive but is also an invasive diagnostic procedure, thus, effective and non-invasive diagnostic methods are urgently needed. Unfortunately, the current methods are not sensitive and specific enough in detecting adenomas and early colorectal neoplasia, hampering treatment and consequently, survival rates. Studies have shown that imbalances in such a relationship which renders the gut microbiota in a dysbiotic state are implicated in the development of adenomas ultimately resulting in CRC. The differences found in the makeup and diversity of the gut microbiota of healthy individuals relative to CRC patients have in recent times gained attention as potential biomarkers in early non-invasive diagnosis of CRC, with promising sensitivity, specificity and even cost-effectiveness. This review summarizes recent studies in the application of these microbiota biomarkers in early CRC diagnosis, limitations encountered in the area of the faecal microbiota studies as biomarkers for CRC, and future research exploits that address these limitations.

Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease.

BACKGROUND: Recent studies reporting the intricate crosstalk between cellular and molecular mediators and the lymphatic endothelium in the development of inflammatory bowel diseases (IBD) suggest altered inflammatory cell drainage and lymphatic vasculature, implicating the lymphatic system as a player in the occurrence, development, and recurrence of intestinal diseases. This article aims to review recent data on the modulatory functions of cellular and molecular components of the IBD microenvironment on the lymphatic system, particularly lymphangiogenesis. It serves as a promising therapeutic target for IBD management and treatment. The interaction with gut microbiota is also explored. MAIN TEXT: Evidence shows that cells of the innate and adaptive immune system and certain non-immune cells participate in the complex processes of inflammatory-induced lymphangiogenesis through the secretion of a wide spectrum of molecular factors, which vary greatly among the various cells. Lymphangiogenesis enhances lymphatic fluid drainage, hence reduced infiltration of immunomodulatory cells and associated-inflammatory cytokines. Interestingly, some of the cellular mediators, including mast cells, neutrophils, basophils, monocytes, and lymphatic endothelial cells (LECs), are a source of lymphangiogenic molecules, and a target as they express specific receptors for lymphangiogenic factors. CONCLUSION: The effective target of lymphangiogenesis is expected to provide novel therapeutic interventions for intestinal inflammatory conditions, including IBD, through both immune and non-immune cells and based on cellular and molecular mechanisms of lymphangiogenesis that facilitate inflammation resolution.

Implications of lymphatic alterations in the pathogenesis and treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by intense immune dysregulation, gut microbiota imbalance, and intestinal epithelium destruction. Among the factors that contribute to the pathogenesis of IBD, lymphatics have received less attention, hence less studied, characterized, and explored. However, in recent years, the role of the lymphatic system in gastrointestinal pathophysiology continues to be highlighted. This paper examines the implications of lymphatic changes in IBD pathogenesis related to immune cells, gut microbiota, intestinal and mesenteric epithelial barrier integrity, and progression to colorectal cancer (CRC). Therapeutic targets of lymphatics in IBD studies are also presented. Available studies indicate that lymph nodes and other secondary lymphatic tissues, provide highly specialized microenvironments for mounting effective immune responses and that lymphatic integrity plays a significant role in small intestine homeostasis, where the lymphatic vasculature effectively controls tissue edema, leukocyte exit, bacterial antigen, and inflammatory chemokine clearance. In IBD, there are functional and morphological alterations in intestinal and mesenteric lymphatic vessels (more profoundly in Crohn's disease [CD] compared to ulcerative colitis [UC]), including lymphangiogenesis, lymphangiectasia, lymphadenopathy, and lymphatic vasculature blockade, affecting not only immunity but gut microbiota and epithelial barrier integrity. While increased lymphangiogenesis is primarily associated with a good prognosis of IBD, increased lymphangiectasia, lymphadenopathy, and lymphatic vessel occlusion correlate with poor prognosis. IBD therapies that target the lymphatic system seek to increase lymphangiogenesis via induction of lymphangiogenic factors and inhibition of its antagonists. The resultant increased lymphatic flow coupled with other anti-inflammatory activities restores gut homeostasis.