What is Gut Health? A Brief Review

Trust your gut, your health depends on it.

INTRODUCTION TO GUT HEALTH

The Gastrointestinal tract (GIT), commonly known as the gut, is considered the most complex organ system in the body¹. It is responsible for the ingestion, processing, and digestion of food as well as for the transport of micronutrients into our bloodstream and, ultimately, to every cell in our body.

The Gastrointestinal tract is composed of the mouth and associated salivary glands, pharynx, oesophagus, stomach, small and large intestines, and rectum. There are also other organs that are tightly associated with the Gastrointestinal tract, including the liver, gallbladder, and pancreas. Jump here, for a more detailed structure of the Gastrointestinal tract.

Dysfunctions of any part of the Gastrointestinal tract can have important consequences on our health. Hence, it pays to understand the main drivers of gut health.

GUT HEALTH KEY FACTORS

There are many factors influencing gut health, including genetics, immune function, and the composition of your gut microbiota. Also, environmental factors like your diet, activity levels and other lifestyle options influence the function and wellbeing of your gut.

If you are ill, chances are your gut health is affected in some way, and you need to get tested to understand what factors are at play. Gut health testing can involve different types of advanced tests, depending on what system is targeted, and requires the help of healthcare specialists.

Some of the most important factors you need to consider when addressing gut health are:

• Genetics

  Your genome is the blueprint that drives all functions in the body, but everyone carries a certain number of genetic mistakes, called mutations, which can affect the function genes, and potentially, proteins in different parts of the body, all of which can affect gut health and health beyond the gut.

  • Certain mutations, for example, can give you a predisposition (an increased chance) to develop gut-related diseases like inflammatory bowel disease (IBD)², Crohn’s disease³, ulcerative colitis⁴, or irritable bowel syndrome (IBS)⁵.
  • Certain genetic mutations can also affect gut health by influencing the way your body responds to some prescription medicines⁶.
  • Advanced genetic testing can reveal the presence of mutations that can potentially cause gut health problems, which can help us design an optimal treatment plan.

• Immune function
  

  The immune system is your body’s defence mechanism against invading pathogens or potentially harmful toxins that enter your body. The immune system also helps clear your body of diseased cells, leading the way for optimal functioning. Malfunction of any portion of the immune system can have serious consequences on your health. Some examples of immune-related conditions include:

  • Autoimmune diseases
    Certain immune diseases result in our own, healthy, cells being targeted and destroyed by the immune system. This is the case of conditions like rheumatoid arthritis, lupus, multiple sclerosis, Type 1 diabetes, psoriasis, hypothyroidism, osteoarthritis, celiac disease, rheumatoid arthritis or Inflammatory bowel disease (IBD), among other conditions.
  • Immune overreactions
    While the role of the immune system is to detect and eliminate potential threats, sometimes this process is faulty. In some diseases, the body overreacts, resulting in an excessive immune reaction. This is the case of conditions like coeliac disease (CD), where the immune system overreacts to the presence of gluten proteins. As a consequence, cells lining the intestinal wall are damaged, causing disease. Another recent example of immune overreaction is being seen in COVID-19 patients. A significant number of deaths associated with this disease is due to an immune overreaction called a cytokine storm, where cytokines, a special type of immune cell, go berserk and harm healthy cells.
  • Chronic inflammation
    This occurs when the body is unable to regulate inflammatory responses, resulting in damage to healthy cells, tissues and organs. Conditions like heart disease, rheumatoid arthritis, type 2 diabetes, obesity and asthma are associated with chronic inflammation.

At our centre, we employ advanced immunological-based testing, the only one currently available in Australia, based on the identification of antibodies against common allergens found in food and other environmental sources. See our article on allergies for more details.

• The Gut Microbiota
  

  Our body is home to trillions of microorganisms, known as the human microbiota, inhabiting every part of our body, inside and out. Most of these microorganisms are found in the small intestine, where they are known as the gut microbiota (GM), and they have several important functions related to gut health and health beyond the gut, like:

  • Helping with the digestion of certain types of foods, like resistant starch, which cannot be digested by our body.
  • Producing chemicals that influence the function of different body systems. These chemicals include certain vitamins that our body needs but can’t produce, as well as short-chain fatty acids and other bacterial metabolites, chemicals that interact with different cells in our body.
  • Interacting with surrounding cells, such as certain immune cells. For example, certain gut microbes are known to regulate the maturation and function of specific immune cells associated with the central nervous system, influencing our body’s response to neuroinflammation, brain injury, autoimmunity, and neurogenesis⁷.

There is currently strong scientific evidence backing important roles for gut microbes in different aspects of our health^7-9. Hence, it is important to understand how well your gut is functioning and whether it needs a bit of help. At the Australian Centre for Functional Medicine, we employ a comprehensive microbiome mapping approach, currently the most advanced DNA-based stool test available in Australia.

SIGNS OF AN ILL GUT

Malfunction of the gut can result in a wide range of symptoms, depending on which cells, tissues or organs are affected. Alterations to your normal composition of gut microbes, known as dysbiosis, whether on your mouth or small intestine, can have a direct effect on gut health, as well as with the health of the rest of your body. Two important locations along the Gastrointestinal tract where microbial dysbiosis occurs and is known to affect health are your mouth and gut.

• Oral microbiota
  

  The mouth is home to more than 600 different species of bacteria, fungi, and viruses, living in the mucosal surfaces of your tongue, cheeks, palate, and tonsils, as well covering your teeth¹². In healthy individuals, this diverse menagerie of microorganisms is maintained in a delicate equilibrium. Alterations to this equilibrium cause dysbiosis, where some species overgrow, causing disease^10-12. Symptoms and conditions associated with oral dysbiosis include:

  • Periodontal or gum disease
    This is an infection of the tissues surrounding your teeth, caused by poor brushing and flossing habits, which leads to an overgrowth of certain microorganisms. Symptoms: Typical symptoms include bad breath, red, swollen or bleeding gums, painful chewing, loose or sensitive teeth and reduced gums, which make your teeth appear longer.
  • Inflammatory bowel disease (IBD)
    This includes Crohn’s disease and ulcerative colitis, two conditions affecting the gastrointestinal tract and gut health. Certain groups of oral bacteria, including members of the bacteria genera Streptococcus, Prevotella, Neisseria, Haemophilus, Veillonella, and Gemella have been shown to be overrepresented in patients with this condition, causing oral dysbiosis. The causes behind IBD are largely unknown but may include diet, genetics, gut dysbiosis, immune malfunction and environmental factors^13-15. Symptoms: Typical symptoms may include diarrhea, fever and fatigue, abdominal pain, bloody stools, poor appetite and weight loss, among others.
  • Rheumatoid arthritis (RA)
    This is an autoimmune disease where our immune system attacks the cell lining of the joints. The causes behind RA are not fully known, but there is a strong genetic component¹⁶. More recently, the gut and oral microbiota have also been linked to RA. In one study, patients with RA exhibited altered microbial composition compared to healthy controls. More specifically, the study found that patients with RA had reduced levels of bacteria of the genus Haemophilus and an overrepresentation of the bacterium Lactobacillus salivarius, in their gut, teeth and saliva, compared to healthy people¹⁷. Symptoms: Typical symptoms of RA include swollen and stiff joints, fatigue, fever and loss of appetite.

• Small Intestine Microbiota
  Harbouring billions of bacteria and other microorganisms, the microbiota living in the small intestine represent the largest and most important portion of our gut microbiota. These microorganisms have been extensively studied and their composition has been linked to multiple aspects of our health^18-21. Some examples of associations between the composition of the small intestine microbiota and our health include:
• • Obesity
    This is a major problem in Australia, affecting as many as 31% of all adults and almost as many children. Recently, studies have established strong links between the composition of the gut microbiota, diet, and genetic factors^22-23. For example, people suffering from obesity-related conditions, such as high adiposity, dysfunctional metabolism of lipids, high blood sugar levels, insulin resistance and dyslipidemia(high levels of lipids in the blood), have been shown to have low bacterial richness. In other words, the gut microbiota of overweight/obese people is composed of a relatively smaller number of species, compared to lean people. This difference holds even when you consider the fact that there is a significant difference in gut microbial composition among healthy people²⁴. Symptoms: overweight and obese persons can suffer from breathlessness, increased sweating, snoring, fatigue, back and joint pains and low self-esteem.
  • Autoimmune disorders
    These conditions occur when our immune system attacks our own, healthy cells. They have mostly unknown causes and are likely to have strong genetic and environmental components. However, recent studies have found strong evidence that the composition of our gut microbiota may also be involved with the development of some autoimmune diseases²⁵. For example, human-based genomic studies have analysed stool samples from people with autoimmune diseases. Their results show strong associations between gut microbial dysbiosis and autoimmune diseases like rheumatoid arthritis^{17, 26}, type 1 diabetes²⁷, multiple sclerosis²⁸ and Inflammatory bowel disease (IBD)²⁹. Symptoms: Depending on the disorder, people suffering from an autoimmune disease can experience swollen and painful joints, abdominal pain, diarrhoea, fatigue, increased thirst and hunger, cognitive decline, vision problems, among many other symptoms.
  • Cardiovascular disease
    This group of diseases include ailments of the heart, high blood pressure, arrhythmia and other problems with blood vessels, affecting over 4.8 million Australians. Worldwide, cardiovascular disease is a major cause of disease and death. The composition of the gut microbiota has been associated with atherosclerosis, atherosclerotic cardiovascular disease, high blood pressure, high cholesterol, coronary artery disease, and arterial stiffness^30-32. Some common cardiovascular diseases include coronary heart disease, heart failure, cardiomyopathy, stroke, and other conditions. Symptoms: typical symptoms can include shortness of breath, chest pain, numbness or pain in legs or arms.
  • Neurological health
    Studies have shown that the composition of the gut microbiota is correlated with depression, autism, Parkinson and Alzheimer’s disease, schizophrenia, anxiety, stress, pain and migraine, multiple sclerosis, and amyotrophic lateral sclerosis³³. This connection between gut microbes and the brain is known as the gut-brain axis. In recent decades, research studies have revealed exciting links, suggesting that the composition of our gut microbes can influence the health of our brain. Symptoms: typical symptoms vary according to each condition, and can include cognitive decline, hallucinations, speech and behaviour disturbances, headache, irritability, tremors in hands, and many others.

Understanding the consequences of gut dysfunction is an important step to discover the best way to deal with a specific medical condition. Another important step is to identify the main drivers of gut dysfunction and gut health.

DRIVERS OF GUT MICROBIAL IMBALANCE

Optimal gut health depends on multiple factors, involving the different organs participating in the process of digesting food and absorbing nutrients. For example, an optimal enzymatic function is essential throughout the Gastrointestinal Tract (GIT).

The Gastrointestinal tract: a primer on function

The digestive functions of the mouth, stomach, pancreas and intestines depend on the optimal production and function of diverse enzymes. In the mouth, the enzyme amylase is responsible for the initial stages of digestion, breaking down starch into more basic components³⁴. The next stage occurs in the stomach, where, gastric acid and proteases enzymes break down proteins and fats³⁵. The pancreas, an accessory organ of the Gastrointestinal tract, produces enzymes like proteases, lipases and amylases that are used in the small intestine³⁶. The final stage of food digestion occurs in the intestines, where multiple enzymes, including pancreatic amylase, trypsin, nucleases, nucleosidases, lipases, peptidase, maltase and lactase further break down food into basic components, which are then absorbed in the small intestine³⁷.

Pathogenesis of the Gastrointestinal tract

There are multiple factors that influence gut health. For example, alterations in the levels and function of the enzymes and acids that govern the process of digestion are an important cause of disease. Changes in the composition of the gut microbiota can also cause health problems. Multiple diseases have been associated with gut microbial dysbiosis, including various intestinal disorders, allergies, asthma, neurological conditions, metabolic diseases, cardiovascular disease, and obesity³⁸.

Below we highlight some examples of factors affecting gut health, their causes and typical symptoms.

Hypochlorhydria

This condition occurs when our stomach produces low levels of gastric acids, and it is characterised by a higher than normal pH in your stomach. A healthy functioning stomach has a pH below 3, highly acid, but the stomach of a person with hypochlorhydria has a pH between 3-5.
Symptoms: typical symptoms someone with hypochlorhydria can experience include bloating, diarrhoea, upset stomach when taking vitamins or supplements, heartburn, fatigue, infections of the Gastrointestinal tract, among other symptoms. Chronic hypochlorhydria can result in digestive problems, nutritional deficiencies, increased risk of bone fracture and developing infections. Conditions like stomach cancer, chronic muscle pain and drug sensitivity have also been associated with hypochlorhydria^39-44.

Low enzyme production

Abnormal levels of digestive enzymes can result in poor absorption of nutrients, due to incomplete food digestion. Symptoms: typical symptoms of this condition include diarrhoea, fatty or loose stools, caused by fat malabsorption, abdominal pain and flatulence⁴⁵. Some conditions associated with long-term low enzyme production include like chronic pancreatitis, cystic fibrosis, celiac disease, diabetes, inflammatory bowel diseases, stomach ulcers, cancer and certain autoimmune diseases^45-48.

Microbial dysbiosis

The Gastrointestinal tract is laced with vast microbial communities, composed of hundreds of different species of microbes, mostly bacteria, but also fungi, viruses and other microorganisms.

• Gut Health: What is a healthy gut microbiota?
  There no specific gut microbial composition that can be defined as a “healthy microbiota”. In fact, studies have found that even among healthy people, there is a lot of variation on the types of gut bacteria present⁴⁹. Instead, what research is showing is that having a rich diversity of gut bugs is what defines a healthy gut. When you are healthy, studies have shown that your gut hosts a large diversity of microbial species, with at least 160 different microbial species found in a single person, according to one study⁵⁰. However, when you are sick, the gut microbiota (GM) diversity is affected⁵¹. Studies have shown that people suffering from conditions like hypertension⁵², Crohn’s disease⁵³, metabolic diseases⁵⁴, or bacterial infections⁵⁵ have reduced diversity of gut bacteria.
• Microbial infections
  Gut health can be affected by infections from pathogenic microbes, such as bacteria, viruses, and parasites. These pathogens can come from many different places. For example, pathogenic bacteria can enter your body through contaminated food or water. One notable example is Helicobacter pylori, a gut pathogen found in as many as 60% of the world population⁵⁶. This bacterium is involved with the development of ulcers, chronic gastritis, and stomach cancer, among other conditions. However, many people carrying this bacterium never develop symptoms. Other important pathogenic microorganisms found in the environment are found in Table 1.
  • Two examples of parasite infections causing disease are Blastocystis hominis and Dientamoeba fragilis two microorganisms commonly found in the intestines of humans. These microorganisms can be acquired through contaminated water or from infected people through a faecal-oral route. In humans, B. hominis and D. fragilis may or may not cause symptoms or disease. Symptoms: In some people, it can cause diarrhea, abdominal pain, nausea, vomiting, fever, fatigue, among other conditions. Treatment to eradicate these species is difficult and should only be undertaken if a patient is suffering from detrimental symptoms. Potential treatments involve antibiotics and other drugs, as well as some probiotics and herbal preparations^57-58
    
• Microbial overgrowth
  Microbial infections can also occur from within your own gut, through the overgrowth of particular microbial species, normally found in the gut at low levels. This is called gut dysbiosis, broadly defined as a status of imbalance in the composition of the gut microbiota. In a gut with gut microbiota (GM) dysbiosis, a gut microbe that is normally innocuous causes harm due to overgrowth. At the same time, your healthy microbial flora is depleted during dysbiosis.
  Another example of microbial dysbiosis that occurs exclusively on the small intestine is known as SIBO or small intestinal bacterial overgrowth. SIBO has been associated with gut health, Inflammatory bowel disease (IBD)⁵⁹, chronic liver disease⁶⁰, irritable bowel syndrome (IBS)⁶¹, chronic pancreatitis⁶², systemic sclerosis⁶³ and other conditions.

Gut microbiota (GM) and other body systems

The Gastrointestinal tract also interacts with multiple other systems in the human body. From the brain to the immune system, our body’s interaction with the gut has been implicated with multiple diseases, including cardiovascular disease, obesity, diabetes, immune disorders, anxiety, depression, and neurological disorders. Some of the most studied systems that interact with the gut microbiota include:

• The Brain and Central Nervous System
  The connection between the gut microbiota and the brain is one of the most studied topics in the past decades. The so-called brain-gut axis refers to the bi-directional communication pathway that connects the gut microbiota with the brain. This pathway involves the vagus nerve, the enteric nervous system, the endocrine and immune systems as well a myriad of chemicals such as short-chain fatty acids, certain amino acids, and peptidoglycans, produced by gut microbes^64-66. Neurological conditions like pain, depression, anxiety, autism, Alzheimer’s diseases (AD), Parkinson’s disease (PD), and stroke have been linked to gut dysbiosis, imbalances that occur in the composition of gut microbiota. For example, people suffering from PD commonly suffer from gut problems, like SIBO, malnutrition, H. pylori infection, and constipation⁶⁷. Other studies have also identified alteration in gut microbiota (GM) composition in people with this disease. Butyrate-producing bacteria and bacteria producing anti-inflammatory compounds, such as Blautia, Coprococcus, and Roseburia, are depleted in the gut of people with PD. In contrast, other bacterial groups, such as H. pylori, E. coli, Ralstonia, Oscillospira and Bacteroides are found in high abundance, compared to healthy people⁶⁸. These findings suggest that gut microbiota (GM) composition may be involved with some aspect of PD development. Comparable findings have been reported for many other neurological conditions, summarised in this table from reference 68.

• The Immune system
  Endowed with the task of protecting our body from pathogens and other potentially harmful invaders, the immune system is a complex organ system that keeps us healthy. Dysfunctions of the immune system can lead to pathogens entering the body and causing disease. Another form of immune dysfunction is autoimmunity when our own, healthy cells are targeted and destroyed by the immune system.
  In recent years, the gut microbiota has been recognised as an important factor in immune function. For example,
  • Many autoimmune disorders, including Type 1 diabetes, multiple sclerosis, rheumatoid arthritis, celiac disease, and asthma are associated with alteration in the gut microbiota (GM) composition^69-73.
  • The gut microbiota (GM) can also influence the function of specific immune cells, through the many metabolites it produces, succinctly presented in this figure, from reference 7.

• The HPA axis
  The hypothalamic-pituitary-adrenal (HPA) axis, along with the sympathetic nervous system, are responsible for the regulation of stress responses. In recent years, a lot of studies have explored how the gut microbiome is connected to the HPA axis. A key finding concerns the role stress has on the composition of the gut microbiota and on the development of the HPA axis. For example, stress is known to affect babies, even before they are born and in their first years of life, influencing the way their HPA axis develops and function, including the production of important hormones, like cortisol.  Studies are now suggesting that gut microbiota (GM) dysbiosis may be a mechanism through which stress affects the HPA axis^64-67.
  The interplay between stress, the HPA axis and the gut microbiota (GM) is an active field of research. Multiple studies show that alterations to HPA function are influenced by gut bacterial dysbiosis, dysfunctions of the intestinal barrier, and inflammation. 
• Other systems
  Recent studies have revealed links between gut health, the gut microbiota (GM) and other organs in the body. For example, researchers are now talking about Gut-Kidney axis. Animal and human-based studies have established links between gut dysbiosis in patients and animal models of hypertension and chronic kidney disease (Table 2)

Table 2. Evidence for the gut-kidney axis. (Adapted from Table 2, Reference 70).

GUT HEALTH TESTING AND TREATMENTS

At the Australian Centre for Functional Medicine, we seek to understand the biology behind the conditions and symptoms you experience. Most importantly, we take a comprehensive approach to improve gut health and your health beyond the gut.

Our main goals are to understand and to cure, not just calming symptoms. Before we can prescribe treatment to cure an ailment, we need to understand the underlying causes behind the ailment. To address this question, we employ advanced diagnostic testing technologies, which allows us to inquire about your health status at multiple levels. Our tests include intestinal permeability screening (blood and urine), breath testing, stool analysis, urine analysis, comprehensive blood testing, metabolic analysis profile, testing for nutrient deficiencies, methylation profile and DNA testing and profiling.

Using this approach, We have successfully treated autoimmune disorders (Addison’s disease, Grave’s disease, celiac disease, rheumatoid arthritis, multiple sclerosis, and others), gut and gut microbiota disorders, nutritional deficiencies, parasite infections, fungal infections, among several other conditions, including:

• Irritable bowel syndrome (IBS)
• Inflammatory bowel disease (IBD)
• Digestive disorders
• Allergy, intolerances, sensitivities
• Infectious diseases
• Food intolerances
• Gut dysbiosis
• Intestinal permeability
• Chronic fatigue
• Skin disorders
• Biotoxins
• Menstruation imbalances

REFERENCES

1. Saffrey MJ. Aging of the mammalian gastrointestinal tract: a complex organ system. Age. 2014 Jun 1;36(3):9603. Read it!
2. Ek WE, D’Amato M, Halfvarson J. The history of genetics in inflammatory bowel disease. Annals of gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology. 2014;27(4):294. Read it!
3. Van Limbergen J, Wilson DC, Satsangi J. The genetics of Crohn’s disease. Annual review of genomics and human genetics. 2009 Sep 22;10:89-116. Read it!
4. Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, Andersen V, Andrews JM, Annese V, Brand S, Brant SR. Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. The Lancet. 2016 Jan 9;387(10014):156-67. Read it!
5. Saito YA, Talley NJ. Genetics of irritable bowel syndrome. The American journal of gastroenterology. 2008 Aug;103(8):2100. Read it!
6. Weinshilboum RM, Wang L. Pharmacogenomics: precision medicine and drug response. In: Mayo Clinic Proceedings 2017 Nov 1 (Vol. 92, No. 11, pp. 1711-1722). Elsevier. Read it!
7. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nature neuroscience. 2017 Feb;20(2):145. Read it!
8. Li Z, Quan G, Jiang X, Yang Y, Ding X, Zhang D, Wang X, Hardwidge PR, Ren W, Zhu G. Effects of metabolites derived from gut microbiota and hosts on pathogens. Frontiers in cellular and infection microbiology. 2018 Sep 14;8:314. Read it!
9. Ridaura V, Belkaid Y. Gut microbiota: the link to your second brain. Cell. 2015 Apr 9;161(2):193-4. Read it!
10. Avila M, Ojcius DM, Yilmaz Ö. The oral microbiota: living with a permanent guest. DNA and cell biology. 2009 Aug 1;28(8):405-11. Read it!
11. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG. The human oral microbiome. Journal of bacteriology. 2010 Oct 1;192(19):5002-17. Read it!
12. Curtis MA, Zenobia C, Darveau RP. The relationship of the oral microbiotia to periodontal health and disease. Cell host & microbe. 2011 Oct 20;10(4):302-6. Read it!
13. Khan I, Ullah N, Zha L, Bai Y, Khan A, Zhao T, Che T, Zhang C. Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome. Pathogens. 2019 Sep;8(3):126. Read it!
14. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. The Lancet. 2007 May 12;369(9573):1627-40. Read it!
15. Said HS, Suda W, Nakagome S, Chinen H, Oshima K, Kim S, Kimura R, Iraha A, Ishida H, Fujita J, Mano S. Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers. DNA research. 2014 Feb 1;21(1):15-25. Read it!
16. Kurkó J, Besenyei T, Laki J, Glant TT, Mikecz K, Szekanecz Z. Genetics of rheumatoid arthritis—a comprehensive review. Clinical reviews in allergy & immunology. 2013 Oct 1;45(2):170-9. Read it!
17. Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nature medicine. 2015 Aug;21(8):895. Read it!
18. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. Bmj. 2018 Jun 13;361:k2179. Read it!
19. Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GA, Gasbarrini A, Mele MC. What is the healthy gut microbiota composition? a changing ecosystem across age, environment, diet, and diseases. Microorganisms. 2019 Jan;7(1):14. Read it!
20. Visconti A, Le Roy CI, Rosa F, Rossi N, Martin TC, Mohney RP, Li W, de Rinaldis E, Bell JT, Venter JC, Nelson KE. Interplay between the human gut microbiome and host metabolism. Nature communications. 2019 Oct 3;10(1):1-0. Read it!
21. Menni C, Valdes AM. Microbiome genetics links short-chain fatty acids to metabolic diseases. Nature Metabolism. 2019 Apr;1(4):420-1. Read it!
22. Sonnenburg JL, Bäckhed F. Diet–microbiota interactions as moderators of human metabolism. Nature. 2016 Jul;535(7610):56-64. Read it!
23. Sun L, Ma L, Ma Y, Zhang F, Zhao C, Nie Y. Insights into the role of gut microbiota in obesity: pathogenesis, mechanisms, and therapeutic perspectives. Protein & cell. 2018 May 1;9(5):397-403. Read it!
24. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013 Aug;500(7464):541-6. Read it!
25. Rosser EC, Mauri C. A clinical update on the significance of the gut microbiota in systemic autoimmunity. Journal of autoimmunity. 2016 Nov 1;74:85-93. Read it!
26. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. elife. 2013 Nov 5;2:e01202. Read it!
27. Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, Queipo-Ortuño MI. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC medicine. 2013 Dec 1;11(1):46. Read it!
28. Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to clostridia XIVa and IV clusters. PloS one. 2015;10(9). Read it!
29. Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut. 2006 Feb 1;55(2):205-11. Read it!
30. Kashtanova D, Tkacheva O, Popenko A, Egshatyan L, Tyakht A, Alexeev D, Kotovskaya Y, Plokhova E, Boytsov S. Gut microbiota and vascular biomarkers in patients without clinical cardiovascular diseases. Artery Research. 2017 Jun 1;18:41-8. Read it!
31. Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nature communications. 2012 Dec 4;3(1):1-8. Read it!
32. Kazemian N, Mahmoudi M, Halperin F, Wu JC, Pakpour S. Gut microbiota and cardiovascular disease: opportunities and challenges. Microbiome. 2020 Dec;8(1):1-7. Read it!
33. Cryan JF, O’Riordan KJ, Cowan CS, Sandhu KV, Bastiaanssen TF, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, Guzzetta KE. The microbiota-gut-brain axis. Physiological reviews. 2019 Oct 1;99(4):1877-2013. Read it!
34. de Almeida PD, Gregio AM, Machado MA, De Lima AA, Azevedo LR. Saliva composition and functions: a comprehensive review. J Contemp Dent Pract. 2008 Mar 1;9(3):72-80.Read it!
35. Schulze K. Imaging and modelling of digestion in the stomach and the duodenum. Neurogastroenterology & Motility. 2006 Mar;18(3):172-83. Read it!
36. Whitcomb DC, Lowe ME. Human pancreatic digestive enzymes. Digestive diseases and sciences. 2007 Jan 1;52(1):1-7. Read it!
37. Pandol SJ. The exocrine pancreas. InColloquium series on integrated systems physiology: from molecule to function 2011 Feb 18 (Vol. 3, No. 1, pp. 1-64). Morgan & Claypool Life Sciences. Read it!
38. Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microbial ecology in health and disease. 2015 Dec 1;26(1):26191. Read it!
39. Kitchen J. Hypochlorhydria: A Review. Townsend Letter for Doctors and Patients. 2001 Nov 1(220):58-. Read it!
40. Tan MC, Graham DY. Proton pump inhibitor therapy after Helicobacter pylori eradication may increase the risk of gastric cancer. BMJ evidence-based medicine. 2018 Jun 1;23(3):111-2. Read it!
41. Kassarjian Z, Russell RM. Hypochlorhydria: a factor in nutrition. Annual review of nutrition. 1989 Jul;9(1):271-85. Read it!
42. Riemer AB, Gruber S, Pali‐Schöll I, Kinaciyan T, Untersmayr E, Jensen‐Jarolim E. Suppression of gastric acid increases the risk of developing Immunoglobulin E‐mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model. Clinical & Experimental Allergy. 2010 Mar;40(3):486-93. Read it!
43. Sarker SA, Ahmed T, Brüssow H. Hunger and microbiology: is a low gastric acid‐induced bacterial overgrowth in the small intestine a contributor to malnutrition in developing countries?. Microbial biotechnology. 2017 Sep;10(5):1025-30. Read it!
44. Sarker SA, Davidsson L, Mahmud H, Walczyk T, Hurrell RF, Gyr N, Fuchs GJ. Helicobacter pylori infection, iron absorption, and gastric acid secretion in Bangladeshi children. The American journal of clinical nutrition. 2004 Jul 1;80(1):149-53. Read it!
45. Ianiro G, Pecere S, Giorgio V, Gasbarrini A, Cammarota G. Digestive enzyme supplementation in gastrointestinal diseases. Current drug metabolism. 2016 Feb 1;17(2):187-93. Read it!
46. Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic pancreatitis and pancreatic cancer risk: a systematic review and meta-analysis. The American journal of gastroenterology. 2017 Sep;112(9):1366. Read it!
47. Gibson‐Corley KN, Meyerholz DK, Engelhardt JF. Pancreatic pathophysiology in cystic fibrosis. The Journal of pathology. 2016 Jan;238(2):311-20. Read it!
48. DiMagno MJ. Exocrine Pancreatic Insufficiency and Pancreatitis Associated with Celiac Disease. Pancreapedia: The Exocrine Pancreas Knowledge Base. 2018 Oct 31. Read it!
49. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007 Oct;449(7164):804-10. Read it!
50. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR. A human gut microbial gene catalogue established by metagenomic sequencing. nature. 2010 Mar;464(7285):59-65. Read it!
51. Morten KJ, Staines-Urias E, Kenyon J. Potential clinical usefulness of gut microbiome testing in a variety of clinical conditions. Human Microbiome Journal. 2018 Oct 1;10. Read it!
52. Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, Zadeh M, Gong M, Qi Y, Zubcevic J, Sahay B. Gut dysbiosis is linked to hypertension. Hypertension. 2015 Jun;65(6):1331-40. Read it!
53. Ni J, Shen TC, Chen EZ, Bittinger K, Bailey A, Roggiani M, Sirota-Madi A, Friedman ES, Chau L, Lin A, Nissim I. A role for bacterial urease in gut dysbiosis and Crohn’s disease. Science translational medicine. 2017 Nov 15;9(416):eaah6888. Read it!
54. Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: Are they linked?. Gut microbes. 2017 Mar 4;8(2):130-42. Read it!
55. Inoue T, Nakayama J, Moriya K, Kawaratani H, Momoda R, Ito K, Iio E, Nojiri S, Fujiwara K, Yoneda M, Yoshiji H. Gut dysbiosis associated with hepatitis C virus infection. Clinical Infectious Diseases. 2018 Aug 31;67(6):869-77. Read it!
56. Hooi JK, Lai WY, Ng WK, Suen MM, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VW, Wu JC, Chan FK. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017 Aug 1;153(2):420-9. Read it!
57. Lepczyńska M, Białkowska J, Dzika E, Piskorz-Ogórek K, Korycińska J. Blastocystis: how do specific diets and human gut microbiota affect its development and pathogenicity?. European Journal of Clinical Microbiology & Infectious Diseases. 2017 Sep 1;36(9):1531-40. Read it!
58. Mokhtar AB, Ahmed SA, Eltamany EE, Karanis P. Anti-Blastocystis Activity In Vitro of Egyptian Herbal Extracts (Family: Asteraceae) with Emphasis on Artemisia judaica. International journal of environmental research and public health. 2019 Jan;16(9):1555. Read it!
59. Shah A, Morrison M, Burger D, Martin N, Rich J, Jones M, Koloski N, Walker MM, Talley NJ, Holtmann GJ. Systematic review with meta‐analysis: the prevalence of small intestinal bacterial overgrowth in inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2019 Mar;49(6):624-35. Read it!
60. Shah A, Shanahan E, Macdonald GA, Fletcher L, Ghasemi P, Morrison M, Jones M, Holtmann G. Systematic review and meta-analysis: prevalence of small intestinal bacterial overgrowth in chronic liver disease. InSeminars in liver disease 2017 Nov (Vol. 37, No. 04, pp. 388-400). Thieme Medical Publishers. Read it!
61. Shah A, Talley NJ, Jones M, Kendall BJ, Koloski N, Walker MM, Morrison M, Holtmann GJ. Small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis of case-control studies. American Journal of Gastroenterology. 2020 Feb 1;115(2):190-201. Read it!
62. Capurso G, Signoretti M, Archibugi L, Stigliano S, Delle Fave G. Systematic review and meta-analysis: small intestinal bacterial overgrowth in chronic pancreatitis. United European gastroenterology journal. 2016 Oct;4(5):697-705. Read it!
63. Pittman N, Rawn SM, Wang M, Masetto A, Beattie KA, Larché M. Treatment of small intestinal bacterial overgrowth in systemic sclerosis: a systematic review. Rheumatology. 2018 Oct 1;57(10):1802-11. Read it!
64. Hergott CB, Roche AM, Tamashiro E, Clarke TB, Bailey AG, Laughlin A, Bushman FD, Weiser JN. Peptidoglycan from the gut microbiota governs the lifespan of circulating phagocytes at homeostasis. Blood, The Journal of the American Society of Hematology. 2016 May 19;127(20):2460-71. Read it!
65. Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut microbes. 2016 May 3;7(3):189-200. Read it!
66. Lin R, Liu W, Piao M, Zhu H. A review of the relationship between the gut microbiota and amino acid metabolism. Amino Acids. 2017 Dec 1;49(12):2083-90. Read it!
67. Felice VD, Quigley EM, Sullivan AM, O’Keeffe GW, O’Mahony SM. Microbiota-gut-brain signalling in Parkinson’s disease: Implications for non-motor symptoms. Parkinsonism & related disorders. 2016 Jun 1;27:1-8. Read it!
68. Zhu S, Jiang Y, Xu K, Cui M, Ye W, Zhao G, Jin L, Chen X. The progress of gut microbiome research related to brain disorders. Journal of Neuroinflammation. 2020 Dec 1;17(1):25. Read it!
69. Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis D. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 2010 Jun 25;32(6):815-27. Read it!
70. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. elife. 2013 Nov 5;2:e01202. Read it!
71. Jamshidi P, Hasanzadeh S, Tahvildari A, et al. Is there any association between gut microbiota and type 1 diabetes? A systematic review. Gut Pathogens. 2019 ;11:49. DOI: 10.1186/s13099-019-0332-7. Read it!
72. Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Soldan MM, Luckey DH, Marietta EV, Jeraldo PR, Chen X, Weinshenker BG. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Scientific reports. 2016 Jun 27;6:28484. Read it!
73. Berer K, Mues M, Koutrolos M, Al Rasbi Z, Boziki M, Johner C, Wekerle H, Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011 Nov;479(7374):538. Read it!
74. Frankiensztajn LM, Elliott E, Koren O. The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders. Current Opinion in Neurobiology. 2020 Jun 1;62:76-82. Read it!
75. Jašarević E, Howard CD, Morrison K, Misic A, Weinkopff T, Scott P, Hunter C, Beiting D, Bale TL. The maternal vaginal microbiome partially mediates the effects of prenatal stress on offspring gut and hypothalamus. Nature neuroscience. 2018 Aug;21(8):1061-71. Read it!
76. Gur TL, Palkar AV, Rajasekera T, Allen J, Niraula A, Godbout J, Bailey MT. Prenatal stress disrupts social behavior, cortical neurobiology and commensal microbes in adult male offspring. Behavioural brain research. 2019 Feb 1;359:886-94. Read it!
77. Jašarević E, Howard CD, Misic AM, Beiting DP, Bale TL. Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner. Scientific reports. 2017 Mar 7;7:44182. Read it!
78. Yang T, Richards EM, Pepine CJ, Raizada MK. The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease. Nature Reviews Nephrology. 2018 Jul;14(7):442-56. Read it!