Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological samples. Metabolomics is emerging as a powerful tool generally for precision medicine. Particularly, integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and disease. However, metabolomics data are very complicated. Preprocessing/pretreating and normalizing procedures on metabolomics data are usually required before statistical analysis. In this review article, we comprehensively review various methods that are used to preprocess and pretreat metabolomics data, including MS-based data and NMR -based data preprocessing, dealing with zero and/or missing values and detecting outliers, data normalization, data centering and scaling, data transformation. We discuss the advantages and limitations of each method. The choice for a suitable preprocessing method is determined by the biological hypothesis, the characteristics of the data set, and the selected statistical data analysis method. We then provide the perspective of their applications in the microbiome and metabolome research.

Long COVID, also known for post-acute sequelae of COVID-19, describes the people who have the signs and symptoms that continue or develop after the acute COVID-19 phase. Long COVID patients suffer from an inflammation or host responses towards the virus approximately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an uncharacterized duration. Anyone infected with COVID-19 before could experience long-COVID conditions, including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early. People with long COVID may experience health problems from different types and combinations of symptoms over time, such as fatigue, dyspnea, cognitive impairments, and gastrointestinal (GI) symptoms (e.g., nausea, vomiting, diarrhea, decreased or loss of appetite, abdominal pain, and dysgeusia). The critical role of the microbiome in these GI symptoms and long COVID were reported in clinical patients and experimental models. Here, we provide an overall view of the critical role of the GI tract and microbiome in the development of long COVID, including the clinical GI symptoms in patients, dysbiosis, viral–microbiome interactions, barrier function, and inflammatory bowel disease patients with long COVID. We highlight the potential mechanisms and possible treatment based on GI health and microbiome. Finally, we discuss challenges and future direction in the long COVID clinic and research.

The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged and is responsible for the Coronavirus Disease 2019 global pandemic. Coronaviruses, including SARS-CoV-2, are strongly associated with respiratory symptoms during infection, but gastrointestinal symptoms, such as diarrhea, vomiting, nausea, and abdominal pain, have been identified in subsets of COVID-19 patients. This article focuses on gastrointestinal symptoms and pathophysiology in COVID-19 disease. Evidence suggests that the gastrointestinal tract could be a viral target for SARS-CoV-2 infection. Not only is the SARS-CoV-2 receptor ACE2 highly expressed in the GI tract and is associated with digestive symptoms, but bleeding and inflammation are observed in the intestine of COVID-19 patients. We further systemically summarize the correlation between COVID-19 disease, gastrointestinal symptoms and intestinal microbiota. The potential oral-fecal transmission of COVID-19 was supported by viral RNA and live virus detection in the feces of COVID-19 patients. Additionally, the viral balance in the GI tract could be disordered during SARS-CoV-2 infection which could further impact the homeostasis of the gut microbial flora. Finally, we discuss the clinical and ongoing trials of treatments/therapies, including antiviral drugs, plasma transfusion and immunoglobulins, and diet supplementations for COVID-19. By reviewing the pathogenesis of SARS-CoV-2 virus, and understanding the correlation among COVID-19, inflammation, intestinal microbiota, and lung microbiota, we provide perspective in prevention and control, as well as diagnosis and treatment of the COVID-19 disease.

The microbiota plays essential roles in health and disease, in both the intestine and the extra-intestine. Dysbiosis of the gut microbiota causes dysfunction in the intestine, which leads to inflammatory, immune, and infectious diseases. Dysbiosis is also associated with diseases beyond the intestine via microbial translocation or metabolisms. The in situ breast microbiome, which may be sourced from the gut through lactation and sexual contact, could be altered and cause breast diseases. In this review, we summarize the recent progress in understanding the interactions among the gut microbiome, breast microbiome, and breast diseases. We discuss the intestinal microbiota, microbial metabolites, and roles of microbiota in immune system. We emphasize the novel roles and mechanisms of the microbiome (both in situ and gastrointestinal sourced) and bacterial products in the development and progression of breast cancer. The intestinal microbial translocation suggests that the gut microbiome is translocated to the skin and subsequently to the breast tissue. The gut bacterial translocation is also due to the increased intestinal permeability. The breast and intestinal microbiota are important factors in maintaining healthy breasts. Micronutrition queuine (Q) is derived from a de novo synthesized metabolite in bacteria. All human cells use queuine and incorporate it into the wobble anticodon position of specific transfer RNAs. We have demonstrated that Q modification regulates genes critical in tight junctions and migration in human breast cancer cells and a breast tumor model. We further discuss the challenges and future perspectives that can move the field forward for prevention, diagnosis, and treatment of breast diseases.

Vitamin D receptor (VDR) executes the main biological functions of its ligand vitamin D. VDR/vitamin D plays critical roles in regulating host immunity, maintaining barrier functions, and shaping gut microbiome. Reduction of intestinal VDR has been reported in various diseases, including inflammatory diseases and colon cancer. However, it is always challenging to get biopsies to test the pathologic changes of VDR in intestine. In the current study, we reported a simple and sensitive quantitative PCR (qPCR) method to detect reduction of intestinal VDR using fecal samples. We validated this method in several experimental models, such as colitis, bacterial infection, and aging. We further correlated the qPCR data of VDR with the protein level of VDR in colon or serum 25 (OH)D₃ in mice with different VDR status (VDR^+/+, VDR^+/-, and VDR^−/−). Our data indicate that the qPCR method to test VDR using fecal samples could detect the expression level of intestinal VDR in various diseases. Our study highlights the feasibility, sensitivity, and simplicity of a molecular method to study the status of VDR as a biomarker.

Fish oil is a natural product that has shown efficacy for managing inflammatory conditions with few side effects. There is emerging evidence that crosstalks between gut epithelial cells and immune cells contribute to chronic infectious diseases. HIV-infected (HIV+) older adults show age-related co-morbidities at a younger age than their uninfected counterparts. Persistent inflammation related to the chronic viral infection and its sequelae is thought to contribute to this disparity. However, little is known about whether fish oil reduces intestinal inflammation in HIV + patients. We measure inflammation and gut barrier function in HIV + older adults (median age = 52, N = 33), following 12 weeks of fish oil supplementation (a total daily dose of 1.6 g of omega-3 fatty acids). We showed a reduction in inflammation and gut permeability as measured by CD14, inflammatory cytokines, lipopolysaccharide, and lipopolysaccharide binding protein. The results indicate that older HIV + adults may benefit from a diet supplemented with the omega-3 fatty acids found in fish oil.

After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.

We know the bad things of dirty environment which is associated with infectious diseases. In this Research Watch, we discuss the good and the unknown of dirty environment, based on a recent Nature paper. We emphasize the role of environment (microbiota) in the development of the human immune system in health and diseases.

Although genes contribute to colorectal cancer, the gut microbiota are an important player. Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression. A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated. Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer. In the current review, we discuss the novel roles of microbiota in the progression of colon cancer. Although microbiota technically include organisms other than bacteria e.g., viruses and fungi, this review will primarily focus on bacteria. We summarize epidemiological studies of human microbiome and colon cancer. We discuss the progress in the scientific understanding of the interplay between the gut microbiota, barrier function, and host responses in experimental models. Further, we discuss the potential application in prevention, diagnosis, and therapy of colon cancer by targeting microbiota. We discuss the challenges lie ahead and the future direction in studying gut microbiome in colon cancer to close the gap between the basic sciences and clinical application.