Endosymbiont

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Endosymbiont

A representation of the endosymbiotic theory

An endosymbiont or endobiont is an organism that lives within the body or cells of another organism. Typically the two organisms are in a mutualistic relationship. Examples are nitrogen-fixing bacteria (called rhizobia), which live in the root nodules of legumes, single-cell algae inside reef-building corals, and bacterial endosymbionts that provide essential nutrients to insects.

Endosymbiosis played key roles in the development of eukaryotes and plants. Roughly 2.2 billion years ago an archaeon absorbed a bacterium through phagocytosis, that eventually became the mitochondria that provide energy to almost all living eukaryotic cells. Approximately 1 billion years ago, some of those cells absorbed cyanobacteria that eventually became chloroplasts, organelles that produce energy from sunlight. Some 100 million years ago, UCYN-A, a nitrogen-fixing bacterium, became an endosymbiont of the marine alga Braarudosphaera bigelowii, eventually evolving into a nitroplast. Similarly, Diatoms in the family Rhopalodiaceae have evolved a diazoplast, a nitrogen-fixing organelle.

Symbionts are either obligate (require their host to survive) or facultative (can survive independently). The most common examples of obligate endosymbiosis are mitochondria and chloroplasts, which reproduce via mitosis in tandem with their host cells. Some human parasites, e.g. Wuchereria bancrofti and Mansonella perstans, thrive in their intermediate insect hosts because of an obligate endosymbiosis with Wolbachia spp. They can both be eliminated by treatments that target their bacterial host.

Etymology

Endosymbiosis comes from the Greek: ἔνδον endon "within", σύν syn "together" and βίωσις biosis "living".

Symbiogenesis

An overview of the endosymbiosis theory of eukaryote origin (symbiogenesis).

Symbiogenesis theory holds that eukaryotes evolved via absorbing prokaryotes. Typically, one organism envelopes a bacterium and the two evolve a mutualistic relationship. The absorbed bacteria (the endosymbiont) eventually lives exclusively within the host cells. This fits the concept of observed organelle development.

Typically the endosymbiont's genome shrinks, discarding genes whose roles are displaced by the host. For example the Hodgkinia genome of Magicicada cicadas is much different from the prior freestanding bacteria. The cicada life cycle involves years of stasis underground. The symbiont produces many generations during this phase, experiencing little selection pressure, allowing their genomes to diversify. Selection is episodic (when the cicadas reproduce). The original Hodgkinia genome split into three much simpler endosymbionts, each encoding only a few genes—an instance of punctuated equilibrium producing distinct lineages. The host requires all three symbionts.

Transmission

Main articles: Horizontal transmission and Vertical transmission

Symbiont transmission is the process where the host acquires its symbiont. Since symbionts are not produced by host cells, they must find their own way to reproduce and populate daughter cells as host cells divide. Horizontal, vertical, and mixed-mode (hybrid of horizonal and vertical) transmission are the three paths for symbiont transfer.

Horizontal

Horizontal symbiont transfer (horizontal transmission) is a process where a host acquires a facultative symbiont from the environment or another host. The Rhizobia-Legume symbiosis (bacteria-plant endosymbiosis) is a prime example of this modality. The Rhizobia-legume symbiotic relationship is important for processes such as the formation of root nodules. It starts with flavonoids released by the legume host, which causes the rhizobia species (endosymbiont) to activate its Nod genes. These Nod genes generate lipooligosaccharide signals that the legume detects, leading to root nodule formation. This process bleeds into other processes such as nitrogen fixation in plants. The evolutionary advantage of such an interaction allows genetic exchange between both organisms involved to increase the propensity for novel functions as seen in the plant-bacterium interaction (holobiont formation).

Vertical

Vertical transmission takes place when the symbiont moves directly from parent to offspring. In horizontal transmission each generation acquires symbionts from the environment. An example is nitrogen-fixing bacteria in certain plant roots, such as pea aphid symbionts. A third type is mixed-mode transmission, where symbionts move horizontally for some generations, after which they are acquired vertically.

Wigglesworthia, a tsetse fly symbiont, is vertically transmitted (via mother's milk). When a symbiont reaches this stage, it resembles a cellular organelle, similar to mitochondria or chloroplasts. In vertical transmission, the symbionts do not need to survive independently, often leading them to have a reduced genome. For instance, pea aphid symbionts have lost genes for essential molecules and rely on the host to supply them. In return, the symbionts synthesize essential amino acids for the aphid host. When a symbiont reaches this stage, it begins to resemble a cellular organelle, similar to mitochondria or chloroplasts. Such dependent hosts and symbionts form a holobiont. In the event of a bottleneck, a decrease in symbiont diversity could compromise host-symbiont interactions, as deleterious mutations accumulate.

Hosts

Invertebrates

The best-studied examples of endosymbiosis are in invertebrates. These symbioses affect organisms with global impact, including Symbiodinium (corals), or Wolbachia (insects). Many insect agricultural pests and human disease vectors have intimate relationships with primary endosymbionts.

Insects

Diagram of cospeciation, where parasites or endosymbionts speciate or branch alongside their hosts. This process is more common in hosts with primary endosymbionts.

Scientists classify insect endosymbionts as Primary or Secondary. Primary endosymbionts (P-endosymbionts) have been associated with their insect hosts for millions of years (from ten to several hundred million years). They form obligate associations and display cospeciation with their insect hosts. Secondary endosymbionts more recently associated with their hosts, may be horizontally transferred, live in the hemolymph of the insects (not specialized bacteriocytes, see below), and are not obligate.

Primary

Among primary endosymbionts of insects, the best-studied are the pea aphid (Acyrthosiphon pisum) and its endosymbiont Buchnera sp. APS, the tsetse fly Glossina morsitans morsitans and its endosymbiont Wigglesworthia glossinidia brevipalpis and the endosymbiotic protists in lower termites. As with endosymbiosis in other insects, the symbiosis is obligate. Nutritionally-enhanced diets allow symbiont-free specimens to survive, but they are unhealthy, and at best survive only a few generations.

In some insect groups, these endosymbionts live in specialized insect cells called bacteriocytes (also called mycetocytes), and are maternally-transmitted, i.e. the mother transmits her endosymbionts to her offspring. In some cases, the bacteria are transmitted in the egg, as in Buchnera; in others like Wigglesworthia, they are transmitted via milk to the embryo. In termites, the endosymbionts reside within the hindguts and are transmitted through trophallaxis among colony members.

Primary endosymbionts are thought to help the host either by providing essential nutrients or by metabolizing insect waste products into safer forms. For example, the putative primary role of Buchnera is to synthesize essential amino acids that the aphid cannot acquire from its diet of plant sap. The primary role of Wigglesworthia is to synthesize vitamins that the tsetse fly does not get from the blood that it eats. In lower termites, the endosymbiotic protists play a major role in the digestion of lignocellulosic materials that constitute a bulk of the termites' diet.

Bacteria benefit from the reduced exposure to predators and competition from other bacterial species, the ample supply of nutrients and relative environmental stability inside the host.

Primary endosymbionts of insects have among the smallest of known bacterial genomes and have lost many genes commonly found in closely related bacteria. One theory claimed that some of these genes are not needed in the environment of the host insect cell. A complementary theory suggests that the relatively small numbers of bacteria inside each insect decrease the efficiency of natural selection in 'purging' deleterious mutations and small mutations from the population, resulting in a loss of genes over many millions of years. Research in which a parallel phylogeny of bacteria and insects was inferred supports the belief that primary endosymbionts are transferred only vertically.

Attacking obligate bacterial endosymbionts may present a way to control their hosts, many of which are pests or human disease carriers. For example, aphids are crop pests and the tsetse fly carries the organism Trypanosoma brucei that causes African sleeping sickness. Studying insect endosymbionts can aid understanding the origins of symbioses in general, as a proxy for understanding endosymbiosis in other species.

The best-studied ant endosymbionts are Blochmannia bacteria, which are the primary endosymbiont of Camponotus ants. In 2018 a new ant-associated symbiont, Candidatus Westeberhardia Cardiocondylae, was discovered in Cardiocondyla. It is reported to be a primary symbiont.

Secondary

Pea aphids are commonly infested by parasitic wasps. Their secondary endosymbionts attack the infesting parasitoid wasp larvae promoting the survival of both the aphid host and its endosymbionts.

The pea aphid (Acyrthosiphon pisum) contains at least three secondary endosymbionts, Hamiltonella defensa, Regiella insecticola, and Serratia symbiotica. Hamiltonella defensa defends its aphid host from parasitoid wasps. This symbiosis replaces lost elements of the insect's immune response.

One of the best-understood defensive symbionts is the spiral bacteria Spiroplasma poulsonii. Spiroplasma sp. can be reproductive manipulators, but also defensive symbionts of Drosophila flies. In Drosophila neotestacea, S. poulsonii has spread across North America owing to its ability to defend its fly host against nematode parasites. This defence is mediated by toxins called "ribosome-inactivating proteins" that attack the molecular machinery of invading parasites. These toxins represent one of the first understood examples of a defensive symbiosis with a mechanistic understanding for defensive symbiosis between an insect endosymbiont and its host.

Sodalis glossinidius is a secondary endosymbiont of tsetse flies that lives inter- and intracellularly in various host tissues, including the midgut and hemolymph. Phylogenetic studies do not report a correlation between evolution of Sodalis and tsetse. Unlike Wigglesworthia, Sodalis has been cultured in vitro.

Cardinium and many other insects have secondary endosymbionts.

Marine

Extracellular endosymbionts are represented in all four extant classes of Echinodermata (Crinoidea, Ophiuroidea, Echinoidea, and Holothuroidea). Little is known of the nature of the association (mode of infection, transmission, metabolic requirements, etc.) but phylogenetic analysis indicates that these symbionts belong to the class Alphaproteobacteria, relating them to Rhizobium and Thiobacillus. Other studies indicate that these subcuticular bacteria may be both abundant within their hosts and widely distributed among the Echinoderms.

Some marine oligochaeta (e.g., Olavius algarvensis and Inanidrillus spp.) have obligate extracellular endosymbionts that fill the entire body of their host. These marine worms are nutritionally dependent on their symbiotic chemoautotrophic bacteria lacking any digestive or excretory system (no gut, mouth, or nephridia).

The sea slug Elysia chlorotica's endosymbiont is the algae Vaucheria litorea. The jellyfish Mastigias have a similar relationship with an algae. Elysia chlorotica forms this relationship intracellularly with the algae's chloroplasts. These chloroplasts retain their photosynthetic capabilities and structures for several months after entering the slug's cells.

Trichoplax have two bacterial endosymbionts. Ruthmannia lives inside the animal's digestive cells. Grellia lives permanently inside the endoplasmic reticulum (ER), the first known symbiont to do so.

Paracatenula is a flatworm which have lived in symbiosis with an endosymbiotic bacteria for 500 million years. The bacteria produce numerous small, droplet-like vesicles that provide the host with needed nutrients.

Dinoflagellates

Dinoflagellate endosymbionts of the genus Symbiodinium, commonly known as zooxanthellae, are found in corals, mollusks (esp. giant clams, the Tridacna), sponges, and the unicellular foraminifera. These endosymbionts capture sunlight and provide their hosts with energy via carbonate deposition.

Previously thought to be a single species, molecular phylogenetic evidence reported diversity in Symbiodinium. In some cases, the host requires a specific Symbiodinium clade. More often, however, the distribution is ecological, with symbionts switching among hosts with ease. When reefs become environmentally stressed, this distribution is related to the observed pattern of coral bleaching and recovery. Thus, the distribution of Symbiodinium on coral reefs and its role in coral bleaching is an important in coral reef ecology.

Phytoplankton

Further information: Microbial loop

In marine environments, endosymbiont relationships are especially prevalent in oligotrophic or nutrient-poor regions of the ocean like that of the North Atlantic. In such waters, cell growth of larger phytoplankton such as diatoms is limited by (insufficient) nitrate concentrations.  Endosymbiotic bacteria fix nitrogen for their hosts and in turn receive organic carbon from photosynthesis. These symbioses play an important role in global carbon cycling.

One known symbiosis between the diatom Hemialus spp. and the cyanobacterium Richelia intracellularis has been reported in North Atlantic, Mediterranean, and Pacific waters. Richelia is found within the diatom frustule of Hemiaulus spp., and has a reduced genome. A 2011 study measured nitrogen fixation by the cyanobacterial host Richelia intracellularis well above intracellular requirements, and found the cyanobacterium was likely fixing nitrogen for its host. Additionally, both host and symbiont cell growth were much greater than free-living Richelia intracellularis or symbiont-free Hemiaulus spp. The Hemaiulus-Richelia symbiosis is not obligatory, especially in nitrogen-replete areas.

Richelia intracellularis is also found in Rhizosolenia spp., a diatom found in oligotrophic oceans. Compared to the Hemaiulus host, the endosymbiosis with Rhizosolenia is much more consistent, and Richelia intracellularis is generally found in Rhizosolenia. There are some asymbiotic (occurs without an endosymbiont) Rhizosolenia, however there appears to be mechanisms limiting growth of these organisms in low nutrient conditions. Cell division for both the diatom host and cyanobacterial symbiont can be uncoupled and mechanisms for passing bacterial symbionts to daughter cells during cell division are still relatively unknown.

Other endosymbiosis with nitrogen fixers in open oceans include Calothrix in Chaetoceros spp. and UNCY-A in prymnesiophyte microalga.  The Chaetoceros-Calothrix endosymbiosis is hypothesized to be more recent, as the Calothrix genome is generally intact. While other species like that of the UNCY-A symbiont and Richelia have reduced genomes. This reduction in genome size occurs within nitrogen metabolism pathways indicating endosymbiont species are generating nitrogen for their hosts and losing the ability to use this nitrogen independently. This endosymbiont reduction in genome size, might be a step that occurred in the evolution of organelles (above).

Protists

Mixotricha paradoxa is a protozoan that lacks mitochondria. However, spherical bacteria live inside the cell and serve the function of the mitochondria. Mixotricha has three other species of symbionts that live on the surface of the cell.

Paramecium bursaria, a species of ciliate, has a mutualistic symbiotic relationship with green alga called Zoochlorella. The algae live in its cytoplasm.

Platyophrya chlorelligera is a freshwater ciliate that harbors Chlorella that perform photosynthesis.

Strombidium purpureum is a marine ciliate that uses endosymbiotic, purple, non-sulphur bacteria for anoxygenic photosynthesis.

Paulinella chromatophora is a freshwater amoeboid that has a cyanobacterium endosymbiont.

Many foraminifera are hosts to several types of algae, such as red algae, diatoms, dinoflagellates and chlorophyta. These endosymbionts can be transmitted vertically to the next generation via asexual reproduction of the host, but because the endosymbionts are larger than the foraminiferal gametes, they need to acquire algae horizontally following sexual reproduction.

Several species of radiolaria have photosynthetic symbionts. In some species the host digests algae to keep the population at a constant level.

Hatena arenicola is a flagellate protist with a complicated feeding apparatus that feeds on other microbes. When it engulfs a green Nephroselmis alga, the feeding apparatus disappears and it becomes photosynthetic. During mitosis the algae is transferred to only one of the daughter cells, while the other cell restarts the cycle.

In 1966, biologist Kwang W. Jeon found that a lab strain of Amoeba proteus had been infected by bacteria that lived inside the cytoplasmic vacuoles. This infection killed almost all of the infected protists. After the equivalent of 40 host generations, the two organisms become mutually interdependent. A genetic exchange between the prokaryotes and protists occurred.

Vertebrates

The spotted salamander (Ambystoma maculatum) lives in a relationship with the algae Oophila amblystomatis, which grows in its egg cases.

Plants

All vascular plants harbor endosymbionts or endophytes in this context. They include bacteria, fungi, viruses, protozoa and even microalgae. Endophytes aid in processes such as growth and development, nutrient uptake, and defense against biotic and abiotic stresses like drought, salinity, heat, and herbivores.

Plant symbionts can be categorized into epiphytic, endophytic, and mycorrhizal. These relations can also be categorized as beneficial, mutualistic, neutral, and pathogenic. Microorganisms living as endosymbionts in plants can enhance their host's primary productivity either by producing or capturing important resources. These endosymbionts can also enhance plant productivity by producing toxic metabolites that aid plant defenses against herbivores.

Plants are dependent on plastid or chloroplast organelles. The chloroplast is derived from a cyanobacterial primary endosymbiosis that began over one billion years ago. An oxygenic, photosynthetic free-living cyanobacterium was engulfed and kept by a heterotrophic protist and eventually evolved into the present intracellular organelle.  

Mycorrhizal endosymbionts appear only in fungi.

Typically, plant endosymbiosis studies focus on a single category or species to better understand their individual biological processes and functions.

Fungal endophytes

Fungal endophytes can be found in all plant tissues. Fungi living below the ground amidst plant roots are known as mycorrhiza, but are further categorized based on their location inside the root, with prefixes such as ecto, endo, arbuscular, ericoid, etc. Fungal endosymbionts that live in the roots and extend their extraradical hyphae into the outer rhizosphere are known as ectendosymbionts.

Arbuscular Mycorrhizal Fungi (AMF)

Arbuscular mycorrhizal fungi or AMF are the most diverse plant microbial endosymbionts. With exceptions such as the Ericaceae family, almost all vascular plants harbor AMF endosymbionts as endo and ecto as well. AMF plant endosymbionts systematically colonize plant roots and help the plant host acquire soil nutrients such as nitrogen. In return it absorbs plant organic carbon products. Plant root exudates contain diverse secondary metabolites, especially flavonoids and strigolactones that act as chemical signals and attracts the AMF. AMF Gigaspora margarita lives as a plant endosymbiont and also harbors further endosymbiont intracytoplasmic bacterium-like organisms. AMF generally promote plant health and growth and alleviate abiotic stresses such as salinity, drought, heat, poor nutrition, and metal toxicity.^[88] Individual AMF species have different effects in different hosts – introducing the AMF of one plant to another plant can reduce the latter's growth.

Endophytic fungi

Endophytic fungi in mutualistic relations directly benefit and benefit from their host plants. They also can help their hosts succeed in polluted environments such as those contaminated with toxic metals. Fungal endophytes are taxonomically diverse and are divided into categories based on mode of transmission, biodiversity, in planta colonization and host plant type. Clavicipitaceous fungi systematically colonize temperate season grasses. Non-clavicipitaceous fungi colonize higher plants and even roots and divide into subcategories. Aureobasidium and preussia species of endophytic fungi isolated from Boswellia sacra produce indole acetic acid hormone to promote plant health and development.

Aphids can be found in most plants. Carnivorous ladybirds are aphid predators and are used in pest control. Plant endophytic fungus Neotyphodium lolii produces alkaloid mycotoxins in response to aphid invasions. In response, ladybird predators exhibited reduced fertility and abnormal reproduction, suggesting that the mycotoxins are transmitted along the food chain and affect the predators.

Endophytic bacteria

Endophytic bacteria belong to a diverse group of plant endosymbionts characterized by systematic colonization of plant tissues. The most common genera include Pseudomonas, Bacillus, Acinetobacter, Actinobacteria, Sphingomonas. Some endophytic bacteria, such as Bacillus amyloliquefaciens, a seed-born endophytic bacteria, produce plant growth by producing gibberellins, which are potent plant growth hormones. Bacillus amyloliquefaciens promotes the taller height of transgenic dwarf rice plants. Some endophytic bacteria genera additionally belong to the Enterobacteriaceae family. Endophytic bacteria typically colonize the leaf tissues from plant roots, but can also enter the plant through the leaves through leaf stomata. Generally, the endophytic bacteria are isolated from the plant tissues by surface sterilization of the plant tissue in a sterile environment. Passenger endophytic bacteria eventually colonize inner tissue of plant by stochastic events while True endophytes possess adaptive traits because of which they live strictly in association with plants. The in vitro-cultivated endophytic bacteria association with plants is considered a more intimate relationship that helps plants acclimatize to conditions and promotes health and growth. Endophytic bacteria are considered to be plant's essential endosymbionts because virtually all plants harbor them, and these endosymbionts play essential roles in host survival. This endosymbiotic relation is important in terms of ecology, evolution and diversity. Endophytic bacteria such as Sphingomonas sp. and Serratia sp. that are isolated from arid land plants regulate endogenous hormone content and promote growth.

Archaea endosymbionts

Archaea are members of most microbiomes. While archaea are abundant in extreme environments, they are less abundant and diverse in association with eukaryotic hosts. Nevertheless, archaea are a substantial constituent of plant-associated ecosystems in the above ground and below ground phytobiome, and play a role in host plant’s health, growth and survival amid biotic and abiotic stresses. However, few studies have investigated the role of archaea in plant health and its symbiotic relationships. Most plant endosymbiosis studies focus on fungal or bacteria using metagenomic approaches.

The characterization of archaea includes crop plants such as rice and maize, but also aquatic plants. The abundance of archaea varies by tissue type; for example archaea are more abundant in the rhizosphere than the phyllosphere and endosphere. This archaeal abundance is associated with plant species type, environment and the plant’s developmental stage. In a study on plant genotype-specific archaeal and bacterial endophytes, 35% of archaeal sequences were detected in overall sequences (achieved using amplicon sequencing and verified by real time-PCR). The archaeal sequences belong to the phyla Thaumarchaeota, Crenarchaeota, and Euryarchaeota.

Bacteria

Some Betaproteobacteria have Gammaproteobacteria endosymbionts.

Fungi

Fungi host endohyphal bacteria; the effects of the bacteria are not well studied. Many such fungi in turn live within plants. These fungi are otherwise known as fungal endophytes. It is hypothesized that the fungi offers a safe haven for the bacteria, and the diverse bacteria that they attract create a micro-ecosystem.

These interactions may impact the way that fungi interact with the environment by modulating their phenotypes. The bacteria do this by altering the fungi's gene expression. For example, Luteibacter sp. has been shown to naturally infect the ascomycetous endophyte Pestalotiopsis sp. isolated from Platycladus orientalis. The Luteibacter sp. influences the auxin and enzyme production within its host, which, in turn, may influence the effect the fungus has on its plant host. Another interesting example of a bacterium living in symbiosis with a fungus is the fungus Mortierella. This soil-dwelling fungus lives in close association with a toxin-producing bacteria, Mycoavidus, which helps the fungus defend against nematodes.

Virus endosymbionts

Main article: Endogenous retrovirus

 

The human genome project found several thousand endogenous retroviruses, endogenous viral elements in the genome that closely resemble and can be derived from retroviruses, organized into 24 families.

Benzo(a)pyrene

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Benzo(a)pyrene

 

Benzo[a]pyrene

Skeletal formula
Ball-and-stick model
Space-filling model
Names
Preferred IUPAC name Benzo[pqr]tetraphene
Other names Benz[a]pyrene Benzo[a]pyrene 3,4-Benzpyrene 3,4-Benzopyrene 3,4-Benz[a]pyrene 3,4-Benzo[a]pyrene Pentacyclo[10.6.2.02,7.09,19.016,20]icosa-1,3,5,7,9,11,13,15,17,19-decaene

Properties
Chemical formula	C20H12
Molar mass	252.316 g·mol−1
Density	1.24 g/cm3 (25 °C)
Melting point	179 °C (354 °F; 452 K)
Boiling point	495 °C (923 °F; 768 K)
Solubility in water	0.2 to 6.2 μg/L
Magnetic susceptibility (χ)	-135.7·10−6 cm3/mol
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H317, H340, H350, H360, H410
Precautionary statements	P201, P202, P261, P272, P273, P280, P281, P302+P352, P308+P313, P321, P333+P313, P363, P391, P405, P501

Benzo[a]pyrene (BaP or B[a]P) is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between 300 °C (572 °F) and 600 °C (1,112 °F). The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, especially grilled meats. The substance with the formula C₂₀H₁₂ is one of the benzopyrenes, formed by a benzene ring fused to pyrene. Its diol epoxide metabolites, more commonly known as BPDE, react with and bind to DNA, resulting in mutations and eventually cancer. It is listed as a Group 1 carcinogen by the IARC. In the 18th century a scrotal cancer of chimney sweepers, the chimney sweeps' carcinoma, was already known to be connected to soot.

Description

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon found in coal tar with the formula C₂₀H₁₂. The compound is one of the benzopyrenes, formed by a benzene ring fused to pyrene, and is the result of incomplete combustion at temperatures between 300 °C (572 °F) and 600 °C (1,112 °F).

Sources

The main source of atmospheric BaP is residential wood burning. It is also found in coal tar, in automobile exhaust fumes (especially from diesel engines), in all smoke resulting from the combustion of organic material (including cigarette smoke), and in charbroiled food. A 2001 National Cancer Institute study found levels of BaP to be significantly higher in foods that were cooked well-done on the barbecue, particularly steaks, chicken with skin, and hamburgers: Cooked meat products have been shown to contain up to 4 ng/g of BaP, and up to 5.5 ng/g in fried chicken and 62.6 ng/g in overcooked charcoal barbecued beef.

BaP is discharged in wastewater by industries such as smelters, particularly iron and steel mills and aluminium smelters.

History

In the 18th century, young British chimney sweeps who climbed into chimneys suffered from chimney sweeps' carcinoma, a scrotal cancer peculiar to their profession, and this was connected to the effects of soot in 1775, in the first work of occupational cancer epidemiology and also the first connection of any chemical mixture to cancer formation. Frequent skin cancers were noted among fuel industry workers in the 19th century. In 1933, BaP was determined to be the compound responsible for these cases, and its carcinogenicity was demonstrated when skin tumors occurred in laboratory animals repeatedly painted with coal tar. BaP has since been identified as a prime carcinogen in cigarette smoke.

Toxicity

Benzo[a]pyrene, showing the base pyrene ring and numbering and ring fusion locations according to IUPAC nomenclature of organic chemistry.

Nervous system

Prenatal exposure of BaP in rats is known to affect learning and memory in rodent models. Pregnant rats eating BaP were shown to negatively affect the brain function in the late life of their offspring. At a time when synapses are first formed and adjusted in strength by activity, BaP diminished NMDA receptor-dependent nerve cell activity measured as mRNA expression of the NMDA NR2B receptor subunit.

Immune system

BaP has an effect on the number of white blood cells, inhibiting some of them from differentiating into macrophages, the body's first line of defense to fight infections. In 2016, the molecular mechanism was uncovered as damage to the macrophage membrane's lipid raft integrity by decreasing membrane cholesterol at 25%. This means less immunoreceptors CD32 (a member of the Fc family of immunoreceptors) could bind to IgG and turn the white blood cell into a macrophage. Therefore, macrophage membranes become susceptible to bacterial infections.

Reproductive system

In experiments with male rats, subchronic exposure to inhaled BaP has been shown to generally reduce the function of testicles and epididymis with lower sex steroid/testosterone production and sperm production.

Carcinogenicity

BaP's metabolites are mutagenic and highly carcinogenic, and it is listed as a Group 1 carcinogen by the IARC. Chemical agents and related occupations, Volume 10, A review of Human Carcinogens, IARC Monographs, Lyon France 2009 

In June 2016, BaP was added as benzo[def]chrysene to the REACH Candidate List of Substances of very high concern for Authorisation.

Numerous studies since the 1970s have documented links between BaP and cancers. It has been more difficult to link cancers to specific BaP sources, especially in humans, and difficult to quantify risks posed by various methods of exposure (inhalation or ingestion). A link between vitamin A deficiency and emphysema in smokers was described in 2005 to be due to BaP, which induces vitamin A deficiency in rats.

A 1996 study provided molecular evidence linking components in tobacco smoke to lung cancer. BaP was shown to cause genetic damage in lung cells that was identical to the damage observed in the DNA of most malignant lung tumours.

Regular consumption of cooked meats has been epidemiologically associated with increased levels of colon cancer (although this in itself does not prove carcinogenicity), A 2005 NCI study found an increased risk of colorectal adenomas was associated with BaP intake, and more strongly with BaP intake from all foods.

The detoxification enzymes cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) are both protective and necessary for benzo[a]pyrene toxicity. Experiments with strains of mice engineered to remove (knockout) CYP1A1 and CYP1B1 reveal that CYP1A1 primarily acts to protect mammals from low doses of BaP, and that removing this protection accumulates large concentrations of BaP. Unless CYP1B1 is also knocked out, toxicity results from the bioactivation of BaP to benzo[a]pyrene -7,8-dihydrodiol-9,10-epoxide, the ultimate toxic compound.

Interaction with DNA

Metabolism of benzo[a]pyrene yielding the carcinogenic benzo[a]pyren-7,8-dihydrodiol-9,10-epoxide.

A DNA adduct (at center) of benzo[a]pyrene, the major mutagen in tobacco smoke.

Properly speaking, BaP is a procarcinogen, meaning that its mechanism of carcinogenesis depends on its enzymatic metabolism to BaP diol epoxide It intercalates in DNA, and the electrophilic epoxide is attacked by nucleophilic guanine bases, forming a bulky guanine adduct.

 

X-ray crystallographic and nuclear magnetic resonance structure studies have shown how this binding distorts the DNA by confusing the double-helical DNA structure. This disrupts the normal process of copying DNA and causes mutations, which explains the occurrence of cancer after exposure. This mechanism of action is similar to that of aflatoxin which binds to the N7 position of guanine.

There are indications that benzo[a]pyrene diol epoxide specifically targets the protective p53 gene. This gene is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor. By inducing G (guanine) to T (thymidine) transversions in transversion hotspots within p53, there is a probability that benzo[a]pyrene diol epoxide inactivates the tumor suppression ability in certain cells, leading to cancer.

Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide is the carcinogenic product of three enzymatic reactions:

1. Benzo[a]pyrene is first oxidized by cytochrome P450 1A1 to form a variety of products, including (+)benzo[a]pyrene-7,8-epoxide.
2. This product is metabolized by epoxide hydrolase, opening up the epoxide ring to yield (−)benzo[a]pyrene-7,8-dihydrodiol.
3. The ultimate carcinogen is formed after another reaction with cytochrome P450 1A1 to yield the (+)benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide. It is this diol epoxide that covalently binds to DNA.

BaP induces cytochrome P450 1A1 (CYP1A1) by binding to the AHR (aryl hydrocarbon receptor) in the cytosol. Upon binding the transformed receptor translocates to the nucleus where it dimerises with ARNT (aryl hydrocarbon receptor nuclear translocator) and then binds xenobiotic response elements (XREs) in DNA located upstream of certain genes. This process increases transcription of certain genes, notably CYP1A1, followed by increased CYP1A1 protein production. This process is similar to induction of CYP1A1 by certain polychlorinated biphenyls and dioxins. Seemingly, CYP1A1 activity in the intestinal mucosa prevents major amounts of ingested benzo[a]pyrene to enter portal blood and systemic circulation. Intestinal, but not hepatic, expression of CYP1A1 depends on TOLL-like receptor 2 (TLR2), which is a eukaryotic receptor for bacterial surface structures such as lipoteichoic acid.

Moreover, BaP has been found to activate a transposon, LINE1, in humans.

Nucleotide excision repair

As illustrated above, (+)benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) forms bulky covalent DNA adducts with guanines. Most of these adducts can be efficiently eliminated from DNA by the process of nucleotide excision repair. Those adducts that are not removed can cause errors during DNA replication leading to carcinogenic mutations.

Intermittent fasting

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Intermittent_fasting

Intermittent fasting is any of various meal timing schedules that cycle between voluntary fasting (or reduced calorie intake) and non-fasting over a given period. Methods of intermittent fasting include alternate-day fasting, periodic fasting, such as the 5:2 diet, and daily time-restricted eating.

Intermittent fasting has been studied to find whether it can reduce the risk of diet-related diseases, such as metabolic syndrome. A 2019 review concluded that intermittent fasting may help with obesity, insulin resistance, dyslipidemia, hypertension, and inflammation. There is preliminary evidence that intermittent fasting is generally safe.

Adverse effects of intermittent fasting have not been comprehensively studied, leading some academics to point out its risk as a dietary fad. The US National Institute on Aging states that there is insufficient evidence to recommend intermittent fasting, and encourages speaking to one's healthcare provider about the benefits and risks before making any significant changes to one's eating pattern.

Fasting exists in various religious practices, including Buddhism, Christianity, Hinduism, Islam, Jainism, and Judaism.

History

Fasting is an ancient tradition, having been practiced by many cultures and religions over centuries.

Therapeutic intermittent fasts for the treatment of obesity have been investigated since at least 1915, with a renewed interest in the medical community in the 1960s after Bloom and his colleagues published an "enthusiastic report". Intermittent fasts, or "short-term starvation periods", ranged from 1 to 14 days in these early studies. This enthusiasm penetrated lay magazines, which prompted researchers and clinicians to caution about the use of intermittent fasts without medical monitoring.

Types

Intermittent fasting calendar for 1 week, alternating feasting days (green), in which the person eats a normal diet, with fasting days (red), in which the person performs intermittent fasting

There are multiple methods of intermittent fasting.

• Time-restricted eating involves eating only during a certain number of hours each day, often establishing a consistent daily pattern of caloric intake within an 8–12-hour time window. This schedule may align food intake with circadian rhythms (establishing eating windows that begin after sunrise and end around sunset).
  • One meal a day fasting is having just one meal a day, and not having anything for the rest of the day.
• Alternate-day fasting involves alternating between a 24-hour "fast day" when the person eats less than 25% of usual energy needs, followed by a 24-hour non-fasting "feast day" period. There are two subtypes:
  • Complete alternate-day fasting is total intermittent energy restriction, where no calories are consumed on fasting days.
  • Modified alternate-day fasting involves partial intermittent energy restriction which allows the consumption of up to 25% of daily calorie needs on fasting days instead of complete fasting. This is akin to alternating days with normal eating and days with a very-low-calorie diet.
• 5:2 diet is a type of periodic fasting (that does not follow a particular food pattern) which focuses entirely on calorie content. In other words, two days of the week are devoted to consumption of approximately 500 to 600 calories, or about 25% of regular daily caloric intake, with normal calorie intake during the other five days of the week. It was first documented in a 2011 article co-authored by Michelle Harvie, Mark Mattson, and 14 additional scientists. It was later published in the UK and Australia by Michael Mosley through the 2012 BBC documentary Eat, Fast and Live Longer (where he learned about the 5:2 diet from Mark Mattson). It also became common in Australia.
• Periodic fasting or whole-day fasting involves intermittent periods of water fasting longer than 24 hours.

The science concerning intermittent fasting is preliminary and uncertain due to an absence of studies on its long-term effects. Preliminary evidence indicates that intermittent fasting may be effective for weight loss, may decrease insulin resistance and fasting insulin, and may improve cardiovascular and metabolic health, although the long term sustainability of these effects has not been studied.

Research

Body weight and metabolic disease risk

There is limited evidence that intermittent fasting produces weight loss comparable to a calorie restricted diet. Most studies on intermittent fasting in humans have observed weight loss, ranging from 2.5% to 9.9%.

The reductions in body weight can be attributed to the loss of fat mass and some lean mass. For time restricted eating the ratio of weight loss is 4:1 for fat mass to lean mass, respectively. Alternate-day fasting does not affect lean body mass, although one review found a small decrease.

Alternate-day fasting improves cardiovascular and metabolic biomarkers similarly to a calorie restriction diet in people who are overweight, obese or have metabolic syndrome. As of 2021, it remains uncertain whether intermittent fasting could prevent cardiovascular disease.

Intermittent fasting has not been studied in children, elderly, or underweight people, and may be harmful in these populations. Intermittent fasting is not recommended for people who are not overweight, and the long-term sustainability of intermittent fasting is unknown as of 2018.

A 2021 review found that moderate alternate-day fasting for two to six months was associated with reductions of body weight, body mass index, and cardiometabolic risk factors in overweight or obese adults.

Other effects

Cancer and other diseases

Intermittent fasting is not recommended to treat cancer in France, the United Kingdom, or the United States, although a few small-scale clinical studies suggest that it may reduce chemotherapy side effects. Periodic fasting may have a minor effect on chronic pain and mood disorders.

Exercise

Athletic performance does not benefit from intermittent fasting. Overnight fasting before exercise increases lipolysis, but reduces performance in prolonged exercise (more than 60 min).

Side effects

There is preliminary evidence that intermittent fasting appears safe for people without diabetes or eating disorders.

Reviews of preliminary clinical studies found that short-term intermittent fasting may produce minor side effects, such as continuous feelings of hunger, irritability, dizziness, nausea, headaches, and impaired thinking, although these effects disappear within a month from beginning the fasting practice. A 2018 systematic review found no major adverse effects. Intermittent fasting is not recommended for pregnant or breastfeeding women, growing children and adolescents, the elderly, or individuals with or vulnerable to eating disorders.

Tolerance

Tolerance of a diet is a determinant of the potential effectiveness and maintenance of benefits obtained, such as weight loss or biomarker improvement. A 2019 review found that drop-out rates varied widely from 2% to 38% for intermittent fasting, and from 0% to 50% for calorie restriction diet.

Possible mechanisms

Preliminary research indicates that fasting may induce a transition through four states:

1. The fed state or absorptive state during satiety, when the primary fuel source is glucose and body fat storage is active, lasting for about 4 hours;
2. The postabsorptive state, lasting for up to 18 hours, when glucagon is secreted and the body uses liver glucose reserves as a fuel source;
3. The fasted state, transitioning progressively to other reserves, such as fat, lactic acid, and alanine, as fuel sources, when the liver glucose reserves are depleted, occurring after 12 to 36 hours of continued fast;
4. The shift from preferential lipid synthesis and fat storage, to the mobilization of fat (in the form of free fatty acids), metabolized into fatty acid-derived ketones to provide energy. Some authors call this transition the "metabolic switch".

A 2019 review of weight-change interventions, including alternate day fasting, time-restricted feeding, exercise and overeating, found that body weight homeostasis could not precisely correct "energetic errors" – the loss or gain of calories – in the short-term.

Another pathway for effects of meal timing on metabolism lies in the influence of the circadian rhythm over the endocrine system, especially on glucose metabolism and leptin. Preliminary studies found that eating when melatonin is secreted – during darkness and commonly when sleeping at night – is associated with increased glucose levels in young healthy adults, and obesity and cardiovascular disorders in less healthy individuals. Reviews on obesity prevention concluded that "meal timing appears as a new potential target in weight control strategies" and suggest that "timing and content of food intake, physical activity, and sleep may be modulated to counteract" circadian and metabolic genetic predispositions to obesity.

Intermittent feeding

Other feeding schemes, such as hypocaloric feeding and intermittent feeding, also called bolus feeding were under study. A 2019 meta-analysis found that intermittent feeding may be more beneficial for premature infants, although better designed studies are required to devise clinical practices. In adults, reviews have not found intermittent feeding to increase glucose variability or gastrointestinal intolerance. A meta-analysis found intermittent feeding had no influence on gastric residual volumes and aspiration, pneumonia, mortality nor morbidity in people with a trauma, but increased the risk of diarrhea.

Food production

Intermittent fasting, or "skip-a-day" feeding, is supposedly the most common feeding strategy for poultry in broiler breeder farms worldwide, as an alternative to adding bulky fibers to the diet to reduce growth. It is perceived as welfare-reducing and thus illegal in several European countries including Sweden. Intermittent fasting in poultry appears to increase food consumption but reduce appetitive behaviors such as foraging.

Religious fasting

Main article: Fasting in religion

Some different types of fastings exist in some religious practices. These include the Black Fast of Christianity (commonly practiced during Lent), Vrata (Hinduism), Ramadan (Islam), Yom Kippur (Judaism), Fast Sunday (The Church of Jesus Christ of Latter-day Saints), Jain fasting, and Buddhist fasting. Religious fasting practices may only require abstinence from certain foods or last for a short period of time and cause negligible effects.

Hinduism

A Vrata/Nombu is observed either as an independent private ritual at a date of one's choice, as part of a particular ceremony such as wedding, or as a part of a major festival such as Diwali (Lakshmi, festival of lights), Shivaratri (Shiva), Navratri (Durga or Rama), Kandasashti (Muruga), Ekadashi (Krishna, Vishnu avatars).

Christianity

In Christianity, many adherents of Christian denominations including Catholics, Lutherans, Methodists, Anglicans, and the Orthodox, often observe the Friday Fast throughout the year, which commonly includes abstinence from meat. Throughout the liturgical season of Lent (and especially on Ash Wednesday and Good Friday) in the Christian calendar, many Christians practice a form of intermittent fasting in which one can consume two collations and one full meal; others partake of the Black Fast, in which no food is consumed until sundown.

Buddhism

In Buddhism, fasting is undertaken as part of the monastic training of Theravada Buddhist monks, who fast daily from noon to sunrise of the next day. This daily fasting pattern may be undertaken by laypeople following the eight precepts.

Islam

During Ramadan, Islamic practices are similar to intermittent fasting by not eating or drinking from dawn until sunset, while permitting food intake in the morning before dawn and in the evening after dusk for 30 days. A meta-analysis on the health of Muslims during Ramadan shows significant weight loss during the fasting period of up to 1.51 kilograms (3.3 lb), but this weight was regained within about two weeks thereafter. The analysis concluded that "Ramadan provides an opportunity to lose weight, but structured and consistent lifestyle modifications are necessary to achieve lasting weight loss." One review found similarities between Ramadan and time-restricted feeding, with the main dissimilarity being the disallowance of water drinking with Islamic fasting. In a 2020 review, Ramadan fasting caused a significant decrease in LDL cholesterol levels, and a slight decline in total cholesterol.

Iftar serving for fasting people in the Imam Reza shrine

A review of the metabolic effects of fasting showed that religious fasting proved to be beneficial in terms of "body weight and glycemia, cardiometabolic risk markers, and oxidative stress parameters", where animals, in the study, that followed a diet regimen consistent with that of religious fasting, were observed to have weight loss in addition to "lowered plasma levels of glucose, triacylglycerols, and insulin growth factor-1". Negative effects of Ramadan fasting include increased risk of hypoglycemia in diabetics, as well as inadequate levels of certain nutrients. Ramadan disallows fluids during the fasting period. This type of fasting would be hazardous for pregnant women, as it is associated with risks of inducing labor and causing gestational diabetes, although it does not appear to affect the child's weight. For these reasons, pregnant women, as well as children who have not reached puberty, the elderly, those who are physically or mentally incapable of fasting, travelers, and breast-feeding mothers are often exempt from religious fasting – Ramadan being one example. Ramadan diurnal intermittent fasting is associated with healthier lifestyle behaviors and a reduction in smoking rate by more than 50% among university students.

Guidelines

United States

The American Heart Association (AHA) says that as with other "popular or fad diets", there is no good evidence of heart health benefits from intermittent fasting.

The American Diabetes Association "found limited evidence about the safety and/or effects of intermittent fasting on type 1 diabetes" and preliminary results of weight loss for type 2 diabetes, and so does not recommend any specific dietary pattern for the management of diabetes until more research is done, recommending instead that "health care providers should focus on the key factors that are common among the patterns".

The National Institute on Aging states that although intermittent fasting showed weight loss success in several studies on obese or overweight individuals, it does not recommend intermittent fasting for non-overweight individuals because of uncertainties about its effectiveness and safety, especially for older adults.

Europe

Given the lack of advantage and the increased incidence of diarrhea, European guidelines do not recommend intermittent feeding for people in intensive care units.

United Kingdom

According to NHS Choices, people considering the 5:2 diet should first consult a physician, as fasting can sometimes be unsafe.

New Zealand

The New Zealand's Ministry of Health considers that intermittent fasting can be advised by doctors to some people, except diabetics, stating that these "diets can be as effective as other energy-restricted diets, and some people may find them easier to stick to" but there are possible side effects during fasting days such as "hunger, low energy levels, light-headedness and poor mental functioning" and note that healthy food must be chosen on non-fasting days.

Usage trends

As of 2019, intermittent fasting was a common fad diet, attracting celebrity endorsements and public interest.

UK and Australia

Intermittent fasting (specifically the 5:2 diet) was popularized by Michael Mosley in the UK and Australia in 2012 after the BBC2 television Horizon documentary Eat, Fast and Live Longer.

North America

In the United States, intermittent fasting became a trend in Silicon Valley, California. It was the most popular diet in 2018, according to a survey by the International Food Information Council.

Commercial activity

As of 2019, interest in intermittent fasting led some companies to commercialize diet coaching, dietary supplements, and full meal packages. These companies were criticized for offering expensive products or services that were not backed by science.