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Alzheimer’s Disease, the Microbiome, and 21st Century Medicine
Published in David Perlmutter, The Microbiome and the Brain, 2019
Nutrient absorption and production represent a sixth mechanism through which the microbiome may impact Alzheimer’s disease risk and pathophysiology, especially type 2 (atrophic) Alzheimer’s disease. Approximately 85% of carbohydrates, 65–95% of proteins, and virtually 100% of fats are absorbed in the upper gut (mostly the proximal small intestine) after being consumed; following this initial digestion, the remaining 10–30% of total ingested caloric potential enters the large intestine (Krajmalnik-Brown et al., 2012). These indigestible carbohydrates and proteins are acted upon by the colonic microbiota, which ferment both resistant and non-resistant starches, unabsorbed sugars, polysaccharides, and mucins, producing short-chain fatty acids (SCFA) such as butyrate, propionate, and acetate, and gases like carbon dioxide, methane, and molecular hydrogen. Branched-chain amino acids add formate, valerate, caproate, isobutyrate, 2-methylbutyrate, and isovalerate to these metabolites (Krajmalnik-Brown et al., 2012). The specifics of SCFA production depend on numerous factors such as age, diet, microbiome, gut transit time, colonic segment, and colonic pH (Ho et al., 2018). Ho noted that specific SCFAs potently interfered with the formation of amyloid-β aggregates, and therefore suggested that these SCFAs may be inhibitory to Alzheimer’s disease pathogenesis. Obesity, another risk factor for Alzheimer’s disease, is also affected by microbiome-associated nutrients and metabolism: molecular hydrogen is produced by the microbiota, and then oxidized by specific microorganisms (methanogens, acetogens, and sulfate reducers), which are overabundant in obese individuals (Krajmalnik-Brown et al., 2012).
Nutrition and the Immune System
Published in David Heber, Zhaoping Li, Primary Care Nutrition, 2017
Fermentation of indigestible carbohydrates is one of the central functions of the human gut microbiota, driving the energy and carbon economy of the colon. Dominant and prevalent species of gut bacteria, including SCFA producers, appear to play a critical role in initial degradation of complex plant-derived polysaccharides (Flint et al. 2012), in conjunction with species that ferment oligosaccharides (e.g., Bifidobacterium), to liberate SCFAs and gases, which are also used as carbon and energy sources by other more specialized bacteria, including reductive acetogens, sulfate-reducing bacteria, and methanogens (which cause the blue flames when some foolish individuals light a match as they produce gas from their anus) (Ze et al. 2013). Efficient conversion of complex indigestible dietary carbohydrates into SCFAs serves microbial cross-feeding communities and the host, with 10% of our daily energy requirements coming from colonic fermentation. Butyrate and propionate can regulate intestinal physiology and immune function, while acetate acts as a substrate for lipogenesis and gluconeogenesis (Macfarlane and Macfarlane 2011). Recently, key roles for these metabolites have been identified in regulating immune function in the periphery; directing appropriate immune response, oral tolerance, and resolution of inflammation; and regulating the inflammatory output of adipose tissue (Arpaia et al. 2013). In the colon, the majority of this carbohydrate fermentation occurs in the proximal colon, at least for people following a Western-style diet. As carbohydrates are broken down and the bolus of undigested material moves distally to the transverse and descending colon, the gut microbiota switches to metabolism of proteins or amino acids. Fermentation of amino acids, besides liberating beneficial SCFAs, produces a range of potentially harmful compounds. Some of these may play a role in gut diseases, such as colon cancer or IBD. Studies in animal models and in vitro show that compounds like ammonia, phenols, p-cresol, certain amines, and hydrogen sulfide play important roles in the initiation or progression of a leaky gut, inflammation, DNA damage, and cancer progression (Windey et al. 2012).
The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health
Published in Gut Microbes, 2021
Ana Nogal, Ana M. Valdes, Cristina Menni
Acetate can be synthesized through two different pathways. Firstly, acetyl-CoA can be produced by decarboxylation of pyruvate, then, acetyl-CoA is hydrolyzed to acetate by an acetyl-CoA hydrolase.80 Most of the acetate is produced by enteric bacteria, including Prevotella spp., Ruminococcus spp., Bifidobacterium spp., Bacteroides spp., Clostridium spp., Streptococcus spp., A. muciniphila, and B. hydrogenotrophica, using this pathway.81 Secondly, the Wood-Ljungdahl pathway can be also used by acetogenic bacteria to form acetate from acetyl-CoA. Here, the reduction of carbon dioxide generates carbon monoxide, which reacts with a coenzyme A molecule and a methyl group to produce acetyl-CoA. At the same time, acetyl-CoA is the substrate to obtain acetate.82
Bile acid oxidation by Eggerthella lenta strains C592 and DSM 2243T
Published in Gut Microbes, 2018
Spencer C. Harris, Saravanan Devendran, Celia Méndez- García, Sean M. Mythen, Chris L. Wright, Christopher J. Fields, Alvaro G. Hernandez, Isaac Cann, Phillip B. Hylemon, Jason M. Ridlon
Prior surveys of the gut of wood-feeding cockroaches40 and acidic fen41 resulted in identification of Eggerthella as encoding a formyl-tetrahydrofolate synthase (fhs) gene, suggesting that Eggerthella may have acetogenic potential. Common to all acetogens are genes encoding acetyl-CoA synthase (ACS)/carbon monoxide dehydrogenase (CODH).42,43 We located a conserved cluster of genes (Elen_3026-3030; CAB18_RS02000-2010) in both E. lenta DSM 2243 and E. lenta C592 which encode 4Fe-4S hybrid cluster proteins which include ACS and CODH. Eggerthella sp. strain YY7918 was found to harbor a different gene cluster, annotated as encoding acsA (EGGYY_24090), ascB/cdhC (EGYY_24100), acsF (BAK45480) providing further genomic evidence that Eggerthella isolates encode WLP genes.
Parabacteroides distasonis: intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health
Published in Gut Microbes, 2021
Jessica C. Ezeji, Daven K. Sarikonda, Austin Hopperton, Hailey L. Erkkila, Daniel E. Cohen, Sandra P. Martinez, Fabio Cominelli, Tomomi Kuwahara, Armand E. K. Dichosa, Caryn E. Good, Michael R. Jacobs, Mikhail Khoretonenko, Alida Veloo, Alexander Rodriguez-Palacios
It is thought that fermentation by P. distasonis results in the production of methane. It is unclear if direct production of methane occurs in P. distasonis; however, it is known that P. distasonis produces hydrogen, carbon dioxide, formic acid, acetic acid, carboxylic acid, and succinic acid.2 Other microbes may convert the carbon dioxide and acetic acid to methane. Acetogenic bacteria might then oxidize the acids, obtaining more acetic acid and either hydrogen or formic acid. Finally, in complex gut communities, methanogens may convert acetic acid to methane.