GUT MICROBIOME DYSBIOSIS IN CHRONIC MALNUTRITION

BUTYRATE PRODUCTON
In relation to colonic disease, butyrate, which results from microbial fermentation, plays a
primarily protective role. It is necessary for the energy metabolism and normal development of colonic
epithelial cells. While specific dietary substrates, for example, resistant starch give off an impression of
being butyrogenic in the colon, it isn't known how much these invigorate butyrate production directly, for
example by advancing amylolytic species, or by implication, for example through cross-feeding of
fermentation items. Cultural and molecular research indicate that highly oxygen-sensitive anaerobes
belonging to Clostridial clusters IV and XIVa are the most common butyrate-producing bacteria in human
feces. These include species that are related to Coprococcus, Eubacterium, Roseburia, and
Faecalibacterium (Pryde, S., et al., 2002).
Because it is the preferred energy source for the colon epithelial cells, contributes to the
maintenance of the gut barrier, and possesses immunomodulatory and anti-inflammatory properties,
butyrate is an essential metabolite in the human colon. (Rivière et al., 2016).
Dysbiosis is portrayed as changes in microbial organization and their metabolites. The anaerobic
fermentation of undigested foods results in the production of numerous metabolites by the gut microbiota.
The primary metabolites, short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate, may offer
significant protection. Butyrate is a four-carbon SCFA that is mostly used as a colonocyte fuel. Some
kinds of cheese, butter, and milk contain small amounts of butyrate as well as dietary fibers like resistant
starch, which is an indirect source of butyrate. Researchers showed that butyrate can absorb into the
portal vein and interconnect with the host body's significant cycles like glucose homeostasis, lipid
digestion and stomach aggravation. Butyrate has been shown in a number of in vitro and in vivo studies to
have metabolic regulation, anti-oxidant, anti-inflammatory, and obesity-fighting properties (Amiri et al.,
2021).
Amiri, P., et al. (2021). Role of butyrate, a gut microbiota derived metabolite, in cardiovascular diseases:
A comprehensive narrative review. Frontiers. Retrieved December 23, 2022, from
https://www.frontiersin.org/articles/10.3389/fphar.2021.837509/full

Microbial fermentation, butyrate and gut health

According to Pryde, S., et al. (2002), although acetate, propionate, and butyrate are all absorbed
by the colonic mucosa, it appears that colonocytes prefer butyrate as their preferred energy source.
Because of its rapid utilization, butyrate concentrations in portal blood are typically undetectable, despite
the fact that approximately 95% of the butyrate produced by colonic bacteria is transported across the
epithelium. Butyrate influences gene expression in addition to its function as a fuel. Specifically, it acts as
a non-competitive inhibitor of histone deacetylases, resulting in hyperacetylation of chromatin. Other
short-chain fatty acids (SCFA) also have these effects, but to a lesser extent. However, specific butyrate
response components have also been discovered. In addition, because it inhibits the transcription factor
NF-B's activation, butyrate has anti-inflammatory effects by reducing the production of proinflammatory
cytokines. The extent of butyrate's effects on gene expression have been more precisely quantified in
recent microarray analyses. Butyrate can act as a trophic factor for cells in intact tissues and induce
apoptosis in tumor cells, depending on its concentration. It can also inhibit growth or promote
differentiation of human cells in tissue culture.
Anaerobic metabolism and butyrate synthesis
Butyrate is constituted from two atoms of acetyl CoA yielding acetoacetyl CoA, which is then
changed over, through the intermediates L(+)- β-hydroxybutyryl CoA and crotonyl CoA, to butyryl CoA.
From there on, butyryl CoA might yield butyrate through butyrate kinase or by means of butyryl CoA:
CoA transferase acetate. Pryde, S., et al. (2002) found that the latter reaction, first found in Clostridium
kluyveri, a soil bacterium, involves the exchange of butyryl CoA for exogenously derived acetate to
produce acetyl CoA and butyrate.
Factors affecting butyrate production in vivo
Substrates that are "butyrogenic," like resistant starch, may have a number of different effects on
the colonic fermentation. Some may alter individual bacteria's fermentative metabolism, for example,
more reduced substrates may tend to encourage butyrate formation due to its role as a hydrogen sink.
Furthermore, microbial population changes are thought to be the cause of most effects. As a result, there
may be direct selection for more species that produce butyrate and are effective primary degraders of the
substrate. However, it is unclear whether active primary degraders are among the predominant butyrate
producers in the case of resistant starch. Alternately, some butyrate producers may be particularly adept at
competing against primary degraders as scavengers of partially degraded substrate, such as
oligosaccharides. Other fermentation products, such as lactate or acetate, which can serve as butyrate
precursors, may also result in an indirect stimulation of butyrate production. Redox potential, mucosal
transport rates, gut turnover and motility, and the fermentation balance of the colonic ecosystem will all
be affected, and certain substrates may directly or indirectly affect these variables. It is important to note
that microbial fermentation in the large intestine is influenced by both dietary and endogenous sources,
with endogenous sources accounting for a significant portion on some diets. (Pryde, S., et al., 2002).
Pryde, S., et al. (2002). Microbiology of butyrate formation in the human colon. OUP Academic.
Retrieved December 22, 2022, from https://academic.oup.com/femsle/article/217/2/133/501025?
login=false

Physiological effect
Only a small amount of butyrate reaches the portal vein and the systemic circulation, where it is
mostly taken up by the colon epithelial cells. The colon epithelial cells prefer to use it as their primary
source of energy. Intestinal effects include lowering the pH of the colon (which decreases the solubility of
bile salts, increases mineral absorption, decreases the absorption of ammonia, and inhibits the growth of
pathogens), stimulating the proliferation of normal colon epithelial cells, inhibiting the proliferation and
apoptosis of colorectal cancer cells, altering the gene expression of colon epithelial cells, and protecting
against colon cancer and colitis. By stimulating the formation of mucin, antimicrobial peptides, and tight-
junction proteins, butyrate essentially enhances the function of the gut barrier. It acts as an anti-
inflammatory agent and interacts with the immune system, stimulates sodium and water absorption also
reduces colon oxidative stress. Other effects include making people feel fuller (Rivière et al., 2016).
Stimulation of butyrate-producing colon bacteria
Since diminished quantities of Bifidobacterium species and butyrate-delivering bacterial species
in the human colon have been accounted for in patients with different disorders and on the grounds that
the Short-chain unsaturated fats (SCFAs) created by these species make valuable impacts, these
microorganisms can potentially prevent disturbances and restore the colon. Consuming probiotics and
prebiotics is one of the most common methods for stimulating bifidobacteria and butyrate-producing
colon bacteria in the human colon (Scott et al., 2015 as cited in Rivière et al., 2016 ).
Rivière, A., et al. (2016). Bifidobacteria and butyrate-producing colon bacteria: Importance and strategies
for their stimulation in the human gut. Frontiers in microbiology. Retrieved December 22, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923077/#:~:text=Butyrate%20is%20an%20essential
%20metabolite,immunomodulatory%20and%20anti%2Dinflammatory%20properties.

Estimation of growth and metabolic capabilities of gut bacterial species

There are trillions of microbes in the human gut, according to previous research, and both the
host and the microbes maintain homeostasis through the exchange of metabolites for health benefits and
other mutual relationships. Some of the most important metabolites derived from the gut microbiota are
SCFAs and branched chain fatty acids (BCFAs), such as acetate, propanoate, butyrate, and isobutyrate,
among others, which significantly contribute to the daily energy requirement, particularly for the
gastrointestinal system's proper development. The researchers discovered that bacteria have a significant
impact on the rate of butyrate production. Pairwise simulation has a higher rate of production than single
species analysis, and this rate is higher in healthy communities among Bangladeshi and Malawian
children, which is consistent with butyrate's beneficial roles. Butyrate may prevent colonic carcinogenesis
and serve as an energy source for intestinal epithelial cells (Beyer-Sehlmeyer et al., 2003; Velázquez et
al., 1996 as cited in Kumar et al., 2018).
Kumar et al. (2018) demonstrated that two short-chain fatty acids (propionate and butyrate) were
found to be significantly higher in the plasma of stunted children compared to the healthy group. This
study demonstrated that there are metabolites elevated in stunted children's plasma.
Kumar, M., et al. (2018). Gut microbiota dysbiosis is associated with malnutrition and reduced plasma
amino acid levels: Lessons from genome-scale metabolic modeling. Metabolic engineering. Retrieved
December 23, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871511/