The term "infectobesity" refers to the hypothesis that obesity in humans can be caused by pathogenic organisms, and the emerging field of medical research that studies the relationship between pathogens and weight gain. The term was coined in 2001 by Dr. Nikhil V. Dhurandhar, at the Pennington Biomedical Research Center.
The study of the effect of infectious agents on metabolism is still in its early stages. Gut flora has been shown to differ between lean and obese humans. There is an indication that gut flora in obese and lean individuals can affect the metabolic potential. This apparent alteration of the metabolic potential is believed to confer a greater capacity to harvest energy contributing to obesity. Whether these differences are the direct cause or the result of obesity has yet to be determined unequivocally. [1]
A possible mechanistic explanation linking gut flora to obesity involves short chain fatty acids. Humans are unable to digest complex polysaccharides and rely on gut microbiota to ferment these polysaccharides into short chain fatty acids. In contrast to polysaccharides, humans can use short chain fatty acids as a source of energy. [2] In addition, research in rodents has indicated that the abundance of short chain fatty acids in the gut can affect the blood levels of gut hormones such as GLP-1, GLP-2 and peptide YY. These changes in gut hormone levels have shown to affect glucose tolerance, insulin signaling, intestinal barrier function and have led to weight gain in rodents. Dietary diversity is associated in humans and animals with a more healthy gut microbiota, and thus may be necessary for effective long-term health improvement strategies, but is often overlooked in animal studies. [3] Furthermore, administration of antibiotics to rodents alters gut microbiota composition and ensuing changes in gut hormone levels are also detected. These results may provide the mechanistic explanation for the claim that antibiotics can lead to obesity in humans. Yet, whether these findings can be replicated in human studies remains to be seen. [4]
An association between viruses and obesity has been found in humans, as well as a number of different animal species. The amount that these associations may have contributed to the rising rate of obesity is yet to be determined. [5] A fat virus is the popular name for the notion that some forms of obesity in humans and animals have a viral source.[ citation needed ]
A carbohydrate is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 and thus with the empirical formula Cm(H2O)n, which does not mean the H has covalent bonds with O. However, not all carbohydrates conform to this precise stoichiometric definition, nor are all chemicals that do conform to this definition automatically classified as carbohydrates.
Dietary fiber or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition, and can be grouped generally by their solubility, viscosity, and fermentability, which affect how fibers are processed in the body. Dietary fiber has two main components: soluble fiber and insoluble fiber, which are components of plant-based foods, such as legumes, whole grains and cereals, vegetables, fruits, and nuts or seeds. A diet high in regular fiber consumption is generally associated with supporting health and lowering the risk of several diseases. Dietary fiber consists of non-starch polysaccharides and other plant components such as cellulose, resistant starch, resistant dextrins, inulin, lignins, chitins, pectins, beta-glucans, and oligosaccharides.
The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.
The Bacillota are a phylum of bacteria, most of which have gram-positive cell wall structure. The renaming of phyla such as Firmicutes in 2021 remains controversial among microbiologists, many of whom continue to use the earlier names of long standing in the literature.
Butyric acid, also known under the systematic name butanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula CH3CH2CH2CO2H. It is an oily, colorless liquid with an unpleasant odor. Isobutyric acid is an isomer. Salts and esters of butyric acid are known as butyrates or butanoates. The acid does not occur widely in nature, but its esters are widespread. It is a common industrial chemical and an important component in the mammalian gut.
Cat food is food specifically designed for consumption by cats. As obligate carnivores, cats have specific requirements for their dietary nutrients, namely nutrients found only in meat, such as taurine, arginine, and Vitamin B6. Certain nutrients, including many vitamins and amino acids, are degraded by the temperatures, pressures and chemical treatments used during manufacture, and hence must be added after manufacture to avoid nutritional deficiency.
Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.
Bacteroides is a genus of Gram-negative, obligate anaerobic bacteria. Bacteroides species are non endospore-forming bacilli, and may be either motile or nonmotile, depending on the species. The DNA base composition is 40–48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids. They also contain meso-diaminopimelic acid in their peptidoglycan layer.
Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract.
Short-chain fatty acids (SCFAs) are fatty acids of two to six carbon atoms. The SCFAs lower limit is interpreted differently, either with 1, 2, 3 or 4 carbon atoms. Derived from intestinal microbial fermentation of indigestible foods, SCFAs in human gut are acetic, propionic and butyric acid. They are the main energy source of colonocytes, making them crucial to gastrointestinal health. SCFAs all possess varying degrees of water solubility, which distinguishes them from longer chain fatty acids that are immiscible.
Free fatty acid receptor 3 protein is a G protein coupled receptor that in humans is encoded by the FFAR3 gene. GPRs reside on cell surfaces, bind specific signaling molecules, and thereby are activated to trigger certain functional responses in their parent cells. FFAR3 is a member of the free fatty acid receptor group of GPRs that includes FFAR1, FFAR2, and FFAR4. All of these FFARs are activated by fatty acids. FFAR3 and FFAR2 are activated by certain short-chain fatty acids (SC-FAs), i.e., fatty acids consisting of 2 to 6 carbon atoms whereas FFFAR1 and FFAR4 are activated by certain fatty acids that are 6 to more than 21 carbon atoms long. Hydroxycarboxylic acid receptor 2 is also activated by a SC-FA that activate FFAR3, i.e., butyric acid.
Free fatty acid receptor 2 (FFAR2), also termed G-protein coupled receptor 43 (GPR43), is a rhodopsin-like G-protein coupled receptor. It is coded by the FFAR2 gene. In humans, the FFAR2 gene is located on the long arm of chromosome 19 at position 13.12. Like other GPCRs, FFAR2s reside on the surface membrane of cells and when bond to one of their activating ligands regulate the function of their parent cells. FFAR2 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes three other receptors which, like FFAR2, are activated by certain fatty acids: FFAR1, FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids whereas FFAR1 and FFAR4 are activated by long-chain fatty acids.
Methanobrevibacter smithii is the predominant archaeon in the microbiota of the human gut. M. smithii has a coccobacillus shape. It plays an important role in the efficient digestion of polysaccharides by consuming the end products of bacterial fermentation. Methanobrevibacter smithii is a single-celled microorganism from the Archaea domain. M. smithii is a methanogen, and a hydrogenotroph that recycles the hydrogen by combining it with carbon dioxide to methane. The removal of hydrogen by M. smithii is thought to allow an increase in the extraction of energy from nutrients by shifting bacterial fermentation to more oxidized end products.
The diet-induced obesity model is an animal model used to study obesity using animals that have obesity caused by being fed high-fat or high-density diets. It is intended to mimic the most common cause of obesity in humans. Typically mice, rats, dogs, or non-human primates are used in these models. These animals can then be used to study in vivo obesity, obesity's comorbidities, and other related diseases. Users of such models must take into account the duration and type of diet as well as the environmental conditions and age of the animals, as each may promote different bodyweights, fat percentages, or behaviors.
Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.
Parasutterella is a genus of Gram-negative, circular/rod-shaped, obligate anaerobic, non-spore forming bacteria from the Pseudomonadota phylum, Betaproteobacteria class and the family Sutterellaceae. Previously, this genus was considered "unculturable," meaning that it could not be characterized through conventional laboratory techniques, such as grow in culture due its unique requirements of anaerobic environment. The genus was initially discovered through 16S rRNA sequencing and bioinformatics analysis. By analyzing the sequence similarity, Parasutterella was determined to be related most closely to the genus Sutterella and previously classified in the family Alcaligenaceae.
The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The "microbiota–gut–brain axis" includes the role of gut microbiota in the biochemical signaling events that take place between the GI tract and the CNS. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.
Microbiota-accessible carbohydrates (MACs) are carbohydrates that are resistant to digestion by a host's metabolism, and are made available for gut microbes, as prebiotics, to ferment or metabolize into beneficial compounds, such as short chain fatty acids. The term, ‘‘microbiota-accessible carbohydrate’’ contributes to a conceptual framework for investigating and discussing the amount of metabolic activity that a specific food or carbohydrate can contribute to a host's microbiota.
The human milk microbiota, also known as human milk probiotics (HMP), refers to the microbiota (community of microorganisms) residing in the human mammary glands and breast milk. Human breast milk has been traditionally assumed to be sterile, but more recently both microbial culture and culture-independent techniques have confirmed that human milk contains diverse communities of bacteria which are distinct from other microbial communities inhabiting the human body.
Bile salt hydrolases (BSH) are microbial enzymes that deconjugate primary bile acids. They catalyze the first step of bile acid metabolism and maintain the bile acid pool for further modification by the microbiota. BSH enzymes play a role in a range of host and microbe functions including host physiology, immunity, and protection from pathogens.
Stable, diverse and healthy GI microbial ecosystems are an important component to consider when using diet to perturb physiological systems in animal models of disease, and it is an aspect often overlooked. A common model to study obesity and insulin resistance is one in which the diet is switched from a basic chow diet to a "Western" or "high fat" diet with a predominance of fat and sugar. Conclusions are typically based on the shift to the calorie dense diet. However, chow diets are classically more diverse. They contain macronutrients from many sources such as whole wheat, dehulled soybean meal, ground corn, animal fat and condensed whey (for example, Purina 5015 Mouse Diet). A common diet used to induce obesity in a mouse is much less diverse such as Research Diets D12492 that contains casein as the source of protein, cornstarch and sucrose as the carbohydrate, and lard as the fat source. The loss of dietary biodiversity may be an important component for the development of obesity that is associated with a narrowing of GI microbiome diversity. Clues to solve another medical mystery are derived from secondary bile acids that are a result of GI microbiota processing. Bariatric procedures such as Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are associated with considerable improvements in co-morbidities of obesity rapidly after the procedure and prior to significant weight loss. Outcomes from RYGB and VSG appear to be related to bile acid signaling through the farnesoid X receptor (FXR) – to regulate physiological systems and also to increase gut permeability by reducing the mucosal barrier. It is now clear that bile acid diversity is dependent on the gut microbial diversity. Expanding dietary fat diversity (for example, saturated-, monounsaturated and polyunsaturated fatty acids) can shift microbiome diversity and thus regulate the bile acid diversity. Additional research into expanding gut microbial richness by dietary diversity is likely to expand concepts in healthy nutrition, stimulate discovery of new diagnostics, and open up novel therapeutic possibilities. In the future, an adult seeking treatment for obesity may be surveyed about dietary preferences and present a stool specimen. Weight loss therapy may begin with a specific dietary plan to widen that person's GI microbiome richness as a prelude to obesity treatments to maintain a weight loss over a long period, as is the case for preadolescent children with obesity and obesity surgery. Indeed, short-term personalized dietary interventions based on a personalized GI microbiome, can improve postprandial glucose regulation in prediabetics and T2D. Already a GI microbiome modulator (GIMM) has been developed and tested to treat prediabetes, which opens new avenues for drug discovery.