Until now, gut microbiota research has primarily centred on samples of faeces, providing insight into the microbial community of the large intestine. However, the small intestine potentially plays an even more crucial role in absorbing nutrients and host–microbe interactions, significantly influencing gut microbiota composition, function and plasticity. Researchers are therefore redirecting their attention to examine how diet, disease and genetic factors influence the microbiota of the small intestine. Understanding the intricate relationship between gut microbes and host immunity offers valuable insight for future research and appears to be critical for optimising the administration of probiotics and harnessing the full potential of manipulating gut microbiota for improving human health.
In the complex world of the human digestive system, trillions of tiny gut microorganisms play a crucial role in maintaining human health – like the conductors of a symphony, orchestrating various aspects of our well-being. When this harmony is disrupted, it can lead to numerous health problems, from metabolic disorders to inflammatory bowel disease and even mental health disorders. Most research on the gut microbiota has focused on studying faecal samples, which represent the contents of the large intestine. However, the small intestine, where nutrients are absorbed, is equally important.
“Remarkably, the microbiota residing in the human small intestine differs significantly from that in the large intestine ecologically and physiologically, but the properties of the microbiota in the small intestine are not well characterised, primarily because of the challenges involved in collecting samples from this part of the digestive tract. Unravelling these interactions could potentially unlock the door to more targeted interventions designed to optimise health and well-being,” explains Benjamin A.H. Jensen, Associate Professor, Department of Biomedical Sciences, University of Copenhagen.
A complex dance of host and microbes
For some time now, scientists have been exploring groundbreaking ways to enhance human health by harnessing the power of gut microbiota. The latest frontier involves administering specially designed probiotics, armed with potent enzymes, to not only protect against unwanted immune responses to these microbial communities but also to aid critical bodily processes, such as individuals who would otherwise be intolerant being able to digest lactose.
“Advanced microbial therapeutics is emerging as hope in combatting various human diseases, and our research focuses on the complex relationship between the host and its bacterial inhabitants in the small and large intestines. But few studies have analysed the microbial composition of the human gut in real life in vivo,” says Benjamin A.H. Jensen.
Recent breakthroughs in sequencing techniques, culturing methods and multiomic approaches have revolutionised the study of host–microbe interactions. However, the knowledge has primarily been confined to faecal samples and colon biopsies, leaving a significant gap in understanding these interactions in the small intestine.
“This is particularly puzzling, since many probiotics target the small intestine, affecting crucial processes such as nutrient absorption. Further, the small intestine’s unique characteristics, including its dynamic microenvironments and the exposed luminal surface because of a loosely adherent mucus layer, make it a prime location for intricate host–microbe interactions,” explains Benjamin A.H. Jensen.
In the small intestine, an abundance of immune cells coexists with reduced mucus secretion, fostering close interactions between the host and these microbes. The researchers, therefore, propose shifting the focus of future research from the colon to the small intestine to uncover valuable insights into how to unlock the full potential of microbiota manipulation.
“Understanding these differences is essential for designing interventions that can precisely target the small intestine, where crucial nutrient absorption occurs and where the complex dance of host–microbe interactions unfolds. This shift in perspective promises to provide critical information that can revolutionise our approach to enhancing microbiota health and ultimately improving overall well-being,” says Benjamin A.H. Jensen.
Diet plays a prominent role
In recent studies, widely different regions of both the small and the large intestine were sampled by various techniques. These consistently reveal distinct microbial communities within the human gastrointestinal tract. One community thrives in the duodenum to the proximal ileum, whereas another dominates the distal ileum to the rectum. This intriguing revelation aligns with recent breakthroughs using ingestible capsule devices, which enabled researchers to sample multiple gastrointestinal regions of 15 healthy individuals during regular digestion.
“Swallowable smart capsules represent a promising option, allowing direct on-site sampling without invasive procedures. The latest advancements in these capsules enable multiomics analysis of the intestinal environment, shedding light on the complicated interactions between microorganisms under physiological conditions,” explains Benjamin A.H. Jensen.
The new studies have profound implications for probiotics. The gastrointestinal tract exhibits fascinating variation in microbial composition along its length and across its various sections – each layer presenting unique challenges and opportunities for administered probiotics.
“This variation could dictate where a probiotic exerts its most significant effects, paving the way for a more tailored approach to harnessing the power of these beneficial microorganisms. Not surprisingly, diet plays a prominent role in shaping the composition and function of the gastrointestinal microbiota, especially in the small intestine,” says Benjamin A.H. Jensen.
Has shown promise
For instance, celiac disease, an inflammatory disorder triggered by gluten consumption by genetically susceptible individuals, has been linked to alterations in the gut microbiota. Probiotic interventions have been proposed to alleviate celiac disease symptoms by restoring microbial balance and reducing the immunogenic properties of gluten.
“However, clinical trials have yielded mixed results, with symptom management appearing more promising than disease prevention, and this might result from differences in the location of the gastrointestinal imbalances and where the probiotics exert their effect,” explains Benjamin A.H. Jensen.
Food allergies provide another intriguing connection between diet and the gastrointestinal microbiota, especially for infants. A disturbed gut microbiota, characterised by reduced levels of certain bacterial species, has been linked to the development of allergies. Restoring the balance of these microbes through bacteriotherapy has shown promise in promoting the growth of immune cells crucial for immune regulation.
“Inflammatory bowel disease presents other significant challenges in gastrointestinal health. The condition is characterised by chronic inflammation and a defective gut lining. Although genetics plays a role, the increasing prevalence of the disease over the years suggests significant environmental influence, including the gut microbiota,” says Benjamin A.H. Jensen.
Standardised sampling needed
One captivating aspect is the ability of the intestinal microbiota to fend off invaders, known as competitive exclusion or colonisation resistance. This defends the host from pathogens and affects probiotics in the gastrointestinal tract. Microbes that grow rapidly or use nutrients effectively gain a competitive edge. Speed, in terms of growth or movement, is a crucial trait for efficient colonisation.
“Intriguingly, amid this competition, intestinal microbes also cooperate. A prime example is cross-feeding, a symbiotic exchange in which metabolites produced by primary fermenters become energy sources for secondary fermenters. This not only fuels the latter but also relieves the former from metabolite inhibition. This collaborative exchange extends to micronutrients, including vitamins,” explains Benjamin A.H. Jensen.
Understanding the mechanisms of probiotic action in different parts of the gastrointestinal tract is vital for harnessing their potential for promoting gut health. However, in the scientific exploration, the details of the small intestine are still mostly hidden. Researchers strongly rely on animal models and gut simulations.
“To unravel the mysteries of the gastrointestinal microbiota and its interactions with the body, especially the small intestine, we are developing advanced tools and models to study the upper gastrointestinal tract. The need for standardised, non-invasive sampling methods with both spatial and temporal resolution remains pressing. So, although previous studies have offered exciting insight, the research into small intestine microbiota is still in its infancy, but the potential appears to be enormous,” concludes Benjamin A.H. Jensen.
