Physical inactivity related changes in human fecal microbiota

Šket, Robert (author), Stres, Blaž (mentor), Debevec, Tadej (comentor)

We explored the assembly of intestinal microbiota in healthy male participants during the randomized crossover design of run-in (5 day) and experimental phases (21-day normoxic bed rest (NBR), hypoxic bed rest (HBR) and hypoxic ambulation (HAmb) (hypoxic ~4000 m simulated altitude)) in a strictly controlled laboratory environment, with balanced fluid and dietary intakes, controlled circadian rhythm, microbial ambiental burden and 24/7 medical surveillance. Intestinal transit spanning Bristol Stool Scale, defecation rates, zonulin, α1-antitrypsin, eosinophil derived neurotoxin, bile acids, reducing sugars, short chain fatty acids, total soluble organic carbon, water content, diet composition and food intake, intestinal electrical conductivity, sterol and polyphenol content and diversity, indole, aromaticity and spectral characteristics of dissolved organic matter, along with nuclear magnetic resonance metabolomics and trace metal makeup of intestinal environment were assessed. Furthermore (i) abundance, structure and diversity of intestinal butyrate producing microbial community sequencing butyrate pathway genes but and buk, (ii) structure and diversity of microbial community sequencing bacterial and archaeal 16S rRNA and (iii) taxonomic and functional description of bacteria, archaea and fungi using shot-gun metagenomics were investigated. Inactivity negatively affected fecal consistency and in combination with hypoxia aggravated the state of gut inflammation (p < 0.05). On the other hand many of the microbial parameters such as butyrate producing microbial community, the general bacterial and archaeal microbial community were shown to lag behind the changes in human physiology and intestinal environment, since significant changes in bacterial community were delayed until week four in HBR only, where members of the genus Bacteroides and proteins involved in iron acquisition and metabolism, cell wall, capsule, virulence and mucin degradation were enriched. This suggest a time-dependent and complex interplay between the host physiology (including apparent constipation), immunity (inflammation), controlled diet, intestinal environment variables and microbiome physiology during the acute cessation of exercise. Finally, yo-yo dieting and active/inactive lifestyle, along with its effects, seems not to be a human peculiarity but rather a common evolutionary adaptation of mammals to survive food shortage and seasons rotation.

• Language: English
• Keywords: human intestinal microbiota, microbial communities, Bacteroides, hypoxia, inactivity inflammation, constipation, gut metabolites
• Work type: Doctoral dissertation
• Typology: 2.08 - Doctoral Dissertation
• Organization: BF - Biotechnical Faculty
• Publisher: [R. Šket]
• Year: 2018
• PID: 20.500.12556/RUL-100755
• UDC: 612.33:579.6:577.121:575.112(043.3)=111
• COBISS.SI-ID: 920951
• Publication date in RUL: 12.04.2018

Secondary language

• Language: Slovenian
• Title: Spremembe humane fekalne mikrobiote povezane s telesno neaktivnostjo

Abstract

Preiskovali smo sestavo črevesne mikrobiote pri zdravih moških preiskovancih v navzkrižno zasnovanem poskusu s 5 dnevnim prilagajanjem na kontrolirano okolje in tremi 21-dnevnimi izvedbami: (i) horizontalnega mirovanja v normoksičnih pogojih (NBR), (ii) horizontalnega mirovanja v hipoksičnih pogojih (HBR) in (iii) gibanja v hipoksičnih pogojih (HAmb) (hipoksično ~ 4000 m simulirane nadmorske višine), v strogo nadzorovanem laboratorijskem okolju, z uravnoteženimi vnosi tekočine in prehrane, kontroliranim cirkadianim ritmom, minimaliziranim mikrobnim vnosom in 24-urnim zdravstvenim nadzorom. Preučevali smo parametre črevesnega okolja: zaprtost črevesja, zonulin, α1-antitripsin, nevrotoksin eozinofilcev, žolčne kisline, reducirajoče sladkorje, kratko-verižne maščobne kisline, vsebnost vode, črevesno električno prevodnost, sterole, polifenole, indol, spektralne lastnosti raztopljenih organskih snovi, celokupne črevesne metabolite in elemente v sledovih. Črevesno mikrobioto smo opredelili glede na: (i) preučevanje številčnosti, strukture in raznovrstnosti mikrobnih skupin, ki proizvajajo masleno kislino, (ii) preučevanje strukture in raznovrstnosti bakterijske in arhejske mikrobiote na osnovi 16S rRNA genov, in (iii) taksonomski ter funkcionalni opis bakterij, arhej in gliv na osnovi sekvenciranja celokupne mikrobne DNA. Telesna neaktivnost je povzročila zaprtje črevesja in v kombinaciji s hipoksijo še poslabšala vnetje v črevesju. Po drugi strani je mikrobiota oz. njen odziv zaostajal za spremembami v človeški fiziologiji in v črevesnem okolju, saj so se bistvene spremembe v bakterijski mikrobioti zgodile v zadnjem tednu poskusa v fiziološko najbolj prizadeti skupini (HBR), kjer je prišlo do obogatitve bakterij rodu Bacteroides in genov vključenih v privzem železa, ter genov za celično steno, kapsulo, virulentnost in razgradnjo mukoznega sloja gostiteljevega črevesja. Slednje kaže na časovno odvisen in zapleten medsebojni vpliv med gostiteljsko fiziologijo (vključno z očitnim zaprtjem), imunskim odgovorom (vnetje črevesja), parametri črevesnega okolja in lastnostmi mikrobiote ob nadzorovanem prehranskem vnosu in med akutnim prenehanjem fizične aktivnosti. Drastične spremembe v prehrani (angl. yo-yo dieting) in nihanje med aktivnim ter neaktivnim življenjskim slogom, ki smo jim priča v vsakdanjem življenju, skupaj s pripadajočimi učinki, niso človeška posebnost, temveč skupna evolucijska prilagoditev sesalcev, razvita kot posledica preživetja zaradi pomanjkanja hrane in prilagajanja na spremembe v letnih časih.

• Keywords: človeška fekalna mikrobiota, mikrobne združbe, Bacteroides, hipoksija, fizična neaktivnost, vnetje, zaprtje, črevesni metaboliti