Probiotics Modulate Host Immune Response and Interact with the Gut Microbiota: Shaping Their Composition and Mediating Antibiotic Resistance.

The consortium of microbes inhabiting the human body, together with their encoded genes and secreted metabolites, is referred to as the "human microbiome." Several studies have established a link between the composition of the microbiome and its impact on human health. This impact spans local gastrointestinal inflammation to systemic autoimmune disorders and neurodegenerative diseases such as Alzheimer's and Autism. Some of these links have been validated by rigorous experiments that identify specific strains as mediators or drivers of a particular condition. Consequently, the development of probiotics to compensate for a missing beneficial microbe(s) has advanced and become popular, especially in the treatment of irritable bowel diseases and to restore disrupted gut flora after antibiotic administration. The widespread use of probiotics is often advocated as a natural ecological therapy. However, this perception is not always accurate, as there is a potential for unexpected interactions when administering live microbial cultures. Here, we designed this research to explore the intricate interactions among probiotics, the host, and microbes through a series of experiments. Our objectives included assessing their immunomodulatory effects, response to oral medications, impact on microbial population dynamics, and mediation of antibiotic resistance. To achieve these goals, we employed diverse experimental protocols, including cell-based enzyme -linked immunosorbent assay (ELISA), antibiotic susceptibility testing, antimicrobial activity assays, computational prediction of probiotic genes responsible for antibiotic resistance, polymerase chain reaction (PCR)-based validation of predicted genes, and survival assays of probiotics in the presence of selected oral medications. Our findings highlight that more than half of the tested probiotics trigger an inflammatory response in the Caco-2 cell line, are influenced by oral medications, exhibit antibacterial activity, and possess genes encoding antimicrobial resistance. These results underscore the necessity for a reevaluation of probiotic usage and emphasize the importance of establishing regulations to govern probiotic testing, approval, and administration.

Microbial dysbiosis in the gut drives systemic autoimmune diseases.

Trillions of microbes survive and thrive inside the human body. These tiny creatures are crucial to the development and maturation of our immune system and to maintain gut immune homeostasis. Microbial dysbiosis is the main driver of local inflammatory and autoimmune diseases such as colitis and inflammatory bowel diseases. Dysbiosis in the gut can also drive systemic autoimmune diseases such as type 1 diabetes, rheumatic arthritis, and multiple sclerosis. Gut microbes directly interact with the immune system by multiple mechanisms including modulation of the host microRNAs affecting gene expression at the post-transcriptional level or production of microbial metabolites that interact with cellular receptors such as TLRs and GPCRs. This interaction modulates crucial immune functions such as differentiation of lymphocytes, production of interleukins, or controlling the leakage of inflammatory molecules from the gut to the systemic circulation. In this review, we compile and analyze data to gain insights into the underpinning mechanisms mediating systemic autoimmune diseases. Understanding how gut microbes can trigger or protect from systemic autoimmune diseases is crucial to (1) tackle these diseases through diet or lifestyle modification, (2) develop new microbiome-based therapeutics such as prebiotics or probiotics, (3) identify diagnostic biomarkers to predict disease risk, and (4) observe and intervene with microbial population change with the flare-up of autoimmune responses. Considering the microbiome signature as a crucial player in systemic autoimmune diseases might hold a promise to turn these untreatable diseases into manageable or preventable ones.

Recent Advances in Understanding the Structure and Function of the Human Microbiome.

Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.