The gastrointestinal tract is a vital organ for maintaining life. It digests and absorbs food, providing essential nutrients to the body and regulating metabolism. Moreover, it employs various mechanisms to maintain homeostasis against external factors like dietary components and gut microbiota. Recent studies have highlighted the significance of these homeostatic mechanisms in relation to both gastrointestinal and non-gastrointestinal diseases, such as obesity, metabolic syndrome, and psychiatric disorders. This is due to the complex interplay between food components, gut microbiota, and the gastrointestinal barrier. The gastrointestinal barrier acts as a defense against external antigens, including gut microbiota and dietary antigens. It comprises physical defenses like the mucin layer and tight junctions, chemical defenses like antimicrobial molecules, and a vast array of immune cells, accounting for approximately 70% of the peripheral immune system.

Non-digestible carbohydrates, such as dietary fiber, are well-known for their physiological effects in creating a “normal state” or maintaining gastrointestinal functions. These effects are induced by changes in the physical and chemical environment of the digestive tract, resulting from the physicochemical properties or fermentation of food components, or by local or remote physiological responses triggered by host recognition of their chemical structure.

Our research group focuses on understanding where and how dietary components, particularly dietary fiber and proteins, influence homeostasis mechanisms, especially the gastrointestinal barrier. We  explore how food components contribute to establishing a normal state through dietary intake.

Mechanism of Goblet Cell Increase by Dietary Fiber Intake and Its Physiological Implications

Disruptions to the gastrointestinal barrier can lead to dysregulation of the gut immune system, often resulting in various diseases and transmucosal infections. Goblet cells in the intestinal epithelium produce and secrete mucus, primarily composed of mucin. This mucus layer acts as a nonspecific barrier, protecting the intestinal epithelium and serving as a reservoir for IgA, thereby preventing the entry of dietary antigens and pathogens. Consequently, changes in mucus production are closely linked to the health of the gastrointestinal barrier.

Our research group has conducted animal experiments to investigate the effects of dietary fiber (DF) on mucin secretion in the small intestine and its physiological implications. We have discovered the following:

• DF intake increases small intestinal mucin secretion in proportion to its bulk (insoluble DF) or viscosity (soluble DF). This increase is achieved by augmenting goblet cell numbers and the metabolic turnover of intestinal epithelial cells, leading to enhanced basal secretion. (Tanabe et al., J Nutr, 2005; Morita et al., J Nutr, 2006; Ito et al., J Nutr, 2009)
• Pectin is an exception to this general rule. It increases small intestinal mucin secretion irrespective of its physical properties, without altering goblet cell numbers. This results in a significant upregulation of jejunal Muc2 expression, suggesting an enhancement of regulatory secretion. (Hino et al., J Nutr, 2012; Hino et al., J Nutr, 2013; Hino et al., JNSV, 2020)
• Mucin secreted in the gastrointestinal tract acts as an endogenous fermentation substrate, promoting the proliferation of regulatory T cells and IgA plasma cells through the formation of the intestinal microbiota and its metabolite, short-chain fatty acids. This contributes to the maintenance of intestinal immune system homeostasis. (Hino et al., J Nutr, 2020)

Based on these findings, we are currently investigating the mechanism underlying the increase of goblet cells by DF intake and its physiological implications. By elucidating the scientific basis for how DF and its fermentation metabolites enhance intestinal barrier function through elevated mucin secretion, we aim to contribute to establishing new nutritional and physiological significance for DF.

Effects of Diet on the Intestinal Microbiota and Its Physiological Implications

The gut microbiota plays a pivotal role in regulating host homeostasis through its metabolite production. A balanced relationship between the host and gut microbiota is essential for optimal health. Various dietary fibers and non-digestible sugars have been promoted as functional foods due to their ability to serve as fermentation substrates for gut microbiota, leading to beneficial physiological effects on the host. However, the digestibility of these foods in the small intestine, or their form of entry into the large intestine, can vary considerably depending on processing methods. These differences in nutrient quality, quantity, and rate of delivery can significantly impact the composition of the gut microbiota, metabolites, and ultimately, host health. By expanding our understanding in this area, we can develop dietary strategies that harness the full potential of gut microbiota.

Effect of Dietary Protein on the Intestinal Microbiota and the Host’s Intestinal Immune System

For the proper maintenance and growth of the intestinal microbiota, it is essential to supply not only dietary fiber and non-digestible sugars as carbon sources but also nitrogen sources and other nutrients that constitute the microbial cells themselves. In other words, we believe that prebiotics solely derived from plant or artificially synthesized polysaccharides are insufficient to sustain the intestinal microbiota’s homeostasis, just as a balanced diet is crucial for human health. This research theme seeks to elucidate the effects of various dietary proteins on the intestinal microbiota and its metabolites by examining the quantity and quality of protein influx into the colon due to differences in dietary proteins. Our goal is to contribute to a deeper understanding of what constitutes a balanced diet for the intestinal microbiota and how dietary proteins influence the homeostasis of the intestinal immune system.

The Impact of Vegetable Particle Size on Gut Microbiota and Short-Chain Fatty Acid Production

The characteristics (amount, type, and shape etc.) of dietary components  reaches the large intestine can vary significantly based on how it’s processed. Our gut microbiota is a community of diverse microbiota, each with unique nutritional needs and growth rates. While this community can maintain a steady state by adapting to changes in our diet, individual microbiota within it can respond differently to these changes. Some microbiota adjust quickly, while others may take longer or be unable to adapt at all. In essence, our gut microbiota is constantly rebalancing itself in response to the various foods we consume. To properly maintain the gut microbiota, it is not only important what we eat (differences in the types and constituent sugars of dietary fiber) but also how we process the food we eat. In this research theme, as a model case, we are investigating the effects of different particle sizes of vegetables, the primary fermentation substrate in the diet, on the gut microbiota and the production of short-chain fatty acids, their metabolites, using an anaerobic culture method with human feces. Through these studies, we aim to clarify the extent to which the gut microbiota is affected by differences in food preparation and processing, and to contribute to the development of dietary strategies that maximize the benefits of gut microbiota.