This thesis reports on the number of individuals in Macrotermes natalensis (Hav.) colonies, their biomass and food consumption in the northern Kruger National Park (KNP). The ecology of M. natalensis is largely undocumented despite the abundance of colonies in southern African savannas. New approaches to mound excavation, sub-sampling and data management are introduced. Via the intracolonial demography of colonies the contribution of each caste in number or proportion is determined. Using this information in combination with body mass and mound density data, biomass per unit area has been computed indicating the importance of this termite in synecology. The measurement of food consumption gives further insight as to how much litter is removed, fragmented and redistributed as nutrients in the ecosystem. Mounds were completely excavated, termites collected by means of vacuuming, and colony size estimated by sub-sampling. It was estimated that, on average, small mounds contain more than 5 000, medium mounds more than 45 000, and large mounds more than 200 000 individual termites. A highly significant relationship between total number of individuals (N ) and mound height (h ) was found, given by lnN = 7.893 + 1.093h (r = 0.92). The proportion of soldiers was found to change as colonies grew larger. In order to derive biomass estimates, a statistical bootstrap procedure was carried out using three databases: body mass, colony population sizes and mound density. Live biomass for small, medium and large mounds was found to be 0.17, 1.40 and 4.16 kg. Dry/wet body mass ratios were established for workers (23.7 %), major soldiers (20.3 %), minor soldiers (35.3 %), nymphs (17.1 %), king (35.4 %) and queen (20.8 %). Average live and dry biomass was calculated to be 0.51 kg/ha (0.051 g/m2) and 0.11 kg/ha (0.011 g/m2). Geology, geomorphology, elevation, local relief, soil patterns and annual rainfall were the abiotic factors shown to be most influential in determining termite biomass, either directly or indirectly. Termite biomass is high in undulating areas where the elevation is 250-400 m, where granitic and rhyolitic soils occur, and where annual rainfall is high (650-700 mm) in the context of the region. Major workers fetch woody litter outside the nest through ingestion into the section of the crop and gizzard. Gut contents were dried, weighed, ashed and reweighed. The ash mainly represents soil particles. The ash-free mass of food that is consumed during a single foraging trip by a foraging individual is 0.166 ± 0.009 mg (CI). Frequency of foraging trips between the mound and food source was observed using translucent tubing. The annual food consumption is given by the formula 365mnp/t , where m = individual mass of ashed crop-gizzard contents, n = number of foraging major workers, p = daily foraging period, and t = individual time spent between nest and food source. Food consumption of this termite in the northern KNP is calculated to be 20.2 kg/ha/yr. It is shown that termites are primary decomposers and contribute to litter fragmentation and the recycling of nutrients into the soil. This thesis gives greater insight into aspects such as colony development, biomass investment and resource utilization of M. natalensis in the northern KNP. / Dissertation (PhD)--University of Pretoria, 2003. / Zoology and Entomology / unrestricted

Les cancers du rein métastatiques résistants aux inhibiteurs de tyrosine kinase peuvent faire l’objet de traitements fondés sur le blocage des points de contrôles immunitaires (ICB). Cependant, les ICB induisent des réponses chez une minorité de patients, et des efforts sont en cours pour identifier les mécanismes à l'origine de la résistance. Les ICB compromettent l'intégrité de la barrière intestinale, affectant ainsi la composition du microbiote, favorisant ainsi soit l'accumulation intestinale, soit la translocation de commensaux immunogènes capables de moduler le tonus immunitaire systémique et de reprogrammer le microenvironnement tumoral. Pour déterminer si des profils microbiens distincts du microbiote intestinal pourraient expliquer la résistance aux ICB, ma thèse a montré que dans une cohorte de 249 patients atteints de cancer traités par ICB que la prescription d’antibiotiques (ATB) a significativement diminué la survie sans progression (PFS) et la survie globale (OS) par rapport aux patients sans ATB. Nous avons confirmé ces données en analysant 121 cencers du rein traités par ICB à Gustave Roussy et 239 cancers du poumon traités par ICB au Memorial Sloan Kettering Cancer Center. Nous avons validé que la dysbiose liée à l'ATB diminue l'activité des ICB. Par la suite, nous avons analysé de manière prospective les microbiotes fécaux de 100 patients atteints de tumeurs sensibles à l'anti-PD-1 en utilisant la métagénomique (MG). Nous avons démontré que les bactéries intestinales présentes avant le traitement anti-PD-1 étaient systématiquement différentes entre les patients qui ont répondu (R) au traitement et les patients qui n’ont pas (NR). Entre les R, nous avons observé une surreprésentation d’Akkermansia muciniphila. Au sein d'une large cohorte de patients RCC (n = 85) traités avec un anticorps anti-PD-1, nous avons analysé le microbiote fécal de 69 patients. Des empreintes de MG spécifiques étaient liées aux meilleures réponses et à la survie sans progression. A. muciniphila et Bacteroides spp étaient plus abondants chez les R. Pour valider la pertinence de ces constatations, nous avons mis en évidence deux principaux éléments de preuve. Premièrement, nous avons démontré que chez les patients atteints de NSCLC, la présence de lymphocytes T CD4 + et CD8 + à mémoire spécifiques de l’IFNγ + vis-à-vis de A. muciniphila prédit une PFS plus longue. Deuxièmement, une transplantation de microbiote fécal (FMT) a été réalisée à l'aide de selles de patient pour recoloniser des souris axéniques ou traitées par ATB dans deux modèles murins. Les matières fécales de R entrainaient une réponse immunitaire plus forte contre la tumeur par rapport aux matières fécales de NR. Ensuite, une supplémentation orale d'A. muciniphila post-FMT avec des matières fécales de NR restaurait l'efficacité de l'anti- PD-1. Dans ce contexte, les cellules dendritiques sécrétaient plus d'IL-12, augmentant le recrutement de lymphocytes T CCR9 + CXCR3 + CD4 + à partir des ganglions lymphatiques mésentériques jusque dans les lits tumoraux, ainsi qu'une augmentation du rapport CD4 + /Treg dans le lit tumoral de souris co-traitées avec mAb anti-PD-1 et A. muciniphila. Enfin, nous avons montré qu'une supplémentation orale avec Bacteroides (B. salyersiae mais pas B. xylanisolvens) ou A. muciniphila pourrait restaurer l'efficacité des ICB dans un modèle FMT- défavorable/dysbiotique". La découverte de bactéries immunogènes capables de prédire et d'accroître les avantages cliniques de l'ICB contribuera au développement de nouveaux outils de biomarqueurs et d'un futur concept thérapeutique, grâce auxquels le traitement du cancer peut être amélioré par la modulation du microbiote intestinal. / Metastatic RCC resistant to tyrosine kinase inhibitors are amenable to new therapies based on immune checkpoint blockade (ICB). However, ICB induces responses in a sizeable minority of patients and efforts are ongoing in order to identify mechanisms driving resistance. ICB compromise the integrity of the intestinal barrier, hereby affecting the composition of the intestinal microbiome, thereby promoting either the intestinal accumulation or the translocation of immunogenic commensals capable of modulating the systemic immune tone and reprogramming the tumor microenvironment. To address whether distinct microbial patterns of the intestinal microbiome could account for the resistance to ICB in RCC, during my PhD I showed in a cohort of 249 patients with cancers treated with ICB that antibiotic (ATB) prescription in a therapeutic window of -2 months up to +1 month after starting ICB significantly decreased progression-free survival (PFS) and overall survival (OS) compared to patients without ATB. We confirmed this data analyzing 121 RCC treated with ICB at Gustave Roussy and 239 NSCLC treated with ICB at Memorial Sloan Kettering Cancer Center. We validated that ATB-related dysbiosis decreases activity of ICB. More precisely, patients in RCC ATB group treated with ICB had a higher rate of primary progressive disease. Subsequently, we prospectively analyzed the fecal microbiomes of 100 patients with tumours amenable to anti-PD-1 mAb using quantitative metagenomics (MG) by shotgun sequencing. We demonstrated that gut bacteria present before anti-PD-1 therapy was consistently different between patients who responded (R) to treatment and patients who did not (NR). In R we observed an overrepresentation of un- and classified Firmicutes. The commensal most significantly associated with favorable clinical outcome and PFS was Akkermansia muciniphila. Within a large cohort of RCC patients (n = 85) treated in the NIVOREN study with anti-PD-1 Ab at Gustave Roussy, we analyzed the fecal microbiome of 69 patients. Specific MG-fingerprints were related to best responses and PFS. A. muciniphila and Bacteroides spp were more abundant in R (Derosa et al. ASCO Merit Award 2018). To validate the relevance of these findings, we brought up two major lines of evidence. First, we demonstrated that in NSCLC patients, the presence of specific IFNγ+ memory CD4+ and CD8+ T cells toward A. muciniphila predicted a longer PFS. Secondly, fecal microbiota transplantation (FMT) was performed using patient feces to recolonize germ-free or ATB-treated mice in two tumor models (MCA-205 and RENCA, the renal cell carcinoma model). Feces from R conveyed a stronger immune response against the tumor compared to feces from NR. Next, in MCA-205 model oral supplementation with A. muciniphila post-FMT with NR feces restored the efficacy of PD-1 Abs. In this setting, dendritic cells secreted more IL-12, increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes from the mesenteric lymph nodes into tumor beds as well as an increase of CD4+/Treg ratio within the tumor bed of mice co-treated with anti-PD-1 mAb and A. muciniphila. Finally, we showed that oral supplementation with Bacteroides (B. salyersiae but not B. xylanisolvens) or A. muciniphila could restore the efficacy of ICB in "unfavorable/dysbiotic" FMT. The discovery of immunogenic bacteria capable of predicting and increasing clinical benefit of ICB will help for the development of novel biomarker tools and a future therapeutic concept, whereby treatment of cancer can be improved by the modulation of gut microbiome.

Au cours des dernières décennies, le régime alimentaire a subi une transition sans précédent, avec une augmentation de la consommation de protéines, de lipides et de glucides simples, et la diminution des apports en fibres. Par ailleurs, au-delà de la composition, la structure des aliments joue un rôle essentiel sur les cinétiques de digestibilité et la biodisponibilité des nutriments, modulant ainsi leur accessibilité pour microbiote dans le côlon. L’impact de la structure d’une matrice alimentaire complexe, formée de protéines et de lipides, sur le microbiote a été analysé de façon intégrée et a montré in vivo que la structure seule, dans le contexte d’un régime équilibré, pouvait altérer la composition du microbiote dans les zones distales et proximales que sont l’iléon et le cæcum. L’émulsion de protéines natives en phase liquide continue avec de fines gouttelettes protéolipidiques a arboré des protéines moins digestibles que l’émulsion de protéines dénaturées, en phase gélifiée, solide, avec de grandes gouttelettes. D’autre part, les lipides de l’émulsion solide étaient, à l’inverse, moins digestibles. Les protéines non digérées de l’émulsion liquide ont favorisé in vivo, les communautés de Lactobacillus et de Copprococcus tout en activant plus fortement les métabolismes de protéolyse. Inversement, les communautés de Bifidobacterium et d’Akkermansia muciniphila ont vu leurs abondances augmenter chez les rats consommant l’émulsion solide. Le deuxième objectif de ce travail de thèse a alors été d'analyser la capacité d'espèces prévalentes du microbiote intestinal humain à métaboliser des protéines non digérées. Nous avons montré, par le suivi des cinétiques de croissance et des productions de métabolites spécifiques, que les protéines du lait étaient une source d'énergie pour B. caccae, P. distasonis, B. longum et B. cocccoides en milieu pauvre ainsi qu'en milieu riche. Dans ces mêmes conditions, le transcriptome de B. caccae a montré la sur-expression de gènes codant pour des peptidases de specifités différentes, pour la production d'indoles, de GABA et de fimbriae. Ces travaux apportent des informations nouvelles sur l'impact de la structure sur l'écosystème digestif, et ouvre des portes pour le développement de nouveaux aliments. / Over the past decades, diet in developed countries has undergone an unprecedented transition, with increased intakes of protein, fat and high glycemic index carbohydrates. The first goal of this PhD work was to investigate how, beyond its composition, the food structure itself could play a part in nutrient digestibility and bioavailability, and consequently modulate the microbiota. We showed in vivo that the structure of proteino-lipidic emulsions modulated peptides transporters, and protein fermentation. The native proteins emulsion in a continuous liquid phase, with fine proteolipid droplets, was less digestible and led to more protein fermentation. It modified the gut microbiota composition in the distal and proximal intestinal sections and increased Lactobacillus and Coprococcus communities. A second in vivo study, using 15N labelled emulsions allowed us to disentangle the digestibility from the transit time effect. The second objective of the PhD was to characterize the capacity of prevalent human gut bacterial species to use undigested proteins as energy source. By monitoring growth kinetics and the production of specific metabolites, we showed that B. caccae, P. distasonis, B. longum et B. cocccoides could use whey protein as energy source. In addition we measured in B. caccae transcriptome, the over-expression of genes encoding for distinct peptidases, but also of GABA and indole pathways, and fimbriae biosynthesis. These data provide new insights on the relationships between food structure and the digestive ecosystem and could lead to the design of new functional food.

Résumé : Les régimes hyperprotéiques sont couramment consommés mais les conséquences au niveau du gros intestin sont peu connues. L’objectif de la thèse était d’étudier les effets des régimes hyperprotéiques et des métabolites bactériens dérivés des acides aminés sur la muqueuse du gros intestinUne série d’expérimentations animales et in vitro a permis de montrer que deux métabolites bactériens dérivés des acides aminés (le sulfure d’hydrogène et le p-cresol) sont toxiques pour l’épithélium lorsqu’ils sont présents en concentration élevée. Les résultats obtenus lors d’une étude clinique montrent que la quantité et la qualité des protéines alimentaires n’ont pas d’effets marqués sur la composition du microbiote fécal mais modifient les concentrations fécales et urinaires en métabolites bactériens.Ces modifications de l’environnement luminal du gros intestin n’étaient pas associées à une augmentation de la cytotoxicité des eaux fécales in vitro. Néanmoins, dans la muqueuse rectale, l’augmentation de l’apport en protéines a régulé l’expression de gènes impliqués dans le maintien de l’homéostasie et ces effets étaient distincts en fonction de la source de protéines utilisée. Toutefois, le niveau d’apport en protéines n’avait pas d’effet sur les paramètres inflammatoires et histologiques dans la muqueuse. Ces résultats ont été complétés par une étude chez le rat montrant qu’un régime hyperprotéique modifie le transcriptome dans les colonocytes mais n’a pas d’effets délétères en termes d’intégrité de l’ADN, de renouvellement de l’épithélium et de fonction barrière. / Abstract: High-protein diets are frequently consumed but the consequences for the large intestine are not well described. The objective of this thesis was to evaluate the effects of high-protein diets and of amino-acid derived bacterial metabolites on the large intestine mucosa. Animal and in vitro studies showed that two amino acid derived bacterial metabolites (hydrogen sulfide and p-cresol) are toxic for the epithelium when present at high concentration. The results obtained in a clinical trial indicate that quantity and quality of dietary protein do not have major effects on the fecal microbiota composition but modify the fecal and urinary concentration of bacterial metabolites.These changes in luminal environment were not associated with an increase in fecal water cytotoxicity in vitro. Nevertheless, in the rectal mucosa, the increase in protein intake regulated the expression of genes implicated in homeostatic processes and these effects were modulated by the source of protein. However, the level of protein intake had no effect on immune and histological parameters in the mucosa. These results were completed with a study in rats showing a clear transcriptome profile in colonocytes induced by a high-protein diet but that was not associated with detrimental effects in terms of DNA integrity, epithelial renewal and barrier function.

No description available.

As of January 2017, the U.S. poultry industry banned the use of antibiotics and now relies on alternatives such as probiotics to help protect animal health. Although probiotic use is not a new concept in the poultry industry, identifying the best combination of bacterial strains to generate an effective probiotic formula requires further investigation. This study aimed to detect a probiotic product of four bacterial strains (Pedioccoccus acidilactici, Pediococcus pentosaceus, Lactobacillus plantarum, and Bacillus subtilis) in a feeding trial with broiler chickens. Birds given the probiotic were predicted to show an improved growth performance with the probiotics colonizing the gut. Ninety-six broiler chickens were equally divided into 3 treatment and 3 control pens. During the 25-day experiment, birds were fed a starter diet (days 0-11) and a grower diet (days 12-25). Experimental birds were administered the probiotic product via the drinking water at a concentration of 3.1×104 CFU/ml. Control birds had an equivalent amount of dextrose filler added to their water supply. Feces were collected hourly on day one and daily thereafter. On days 1, 22, and 25 of the experiment, 2 birds from each pen were euthanized for gut sampling. Lumen and mucosa samples were collected from the duodenum, jejunum, ileum, and ceca. Species-specific and strain specific PCR primers were employed for probiotic detection. Wild strains of P. acidilactici, P. pentosaceus, and L. plantarum were detected in the feeds, inhibiting detection of the probiotic strains when using species-specific PCR primers. Strain-specific primers were used to detect the probiotic Pedioccoccus acidilactici and Lactobacillus plantarum strains. B. subtilis was detected in feces within one hour of probiotic administration and was predominantly detected in experimental birds only. Both P. acidilactici and L. plantarum probiotic strains were initially detected in the feces of treated birds within two hours of probiotic administration and again ten days later. Both L. plantarum and B. subtilis were seen only in treated bird gut samples. L. plantarum was predominantly detected in the ceca near the end of the small intestine. P. pentosaceus was observed more often in treated gut samples and P. acidilactici was the least commonly detected probiotic strain. All administered bacteria were rarely seen in mucosa samples. Feed-endogenous P. acidilactici and L. plantarum strains became progressively more detectable in the mucosa along the gastrointestinal tract suggesting gut colonization, however, probiotic strains did not appear to colonize the mucosa of treated birds. Although probiotic strains were no longer detected after product removal, all probiotic strains were detected in feces and gut samples during probiotic administration, suggesting the bacteria can colonize the gut. Probiotic supplementation did not result in significant differences in body weight gain, feed intake, or feed conversion ratio. However, birds growing in a more stressful environment than the carefully controlled experimental set up used here may show probiotic-related effects. This study identified that the probiotic bacteria appeared to survive the gastrointestinal tract, exhibited a transit time of 1-2 hours, could possibly colonize chickens, and localized near the end of the chicken gut.

Various disorders closely linked to gut dysbiosis have been associated with poor dietary patterns. Dietary prebiotic fibers play an essential role in modulating the gut microbiome by enhancing the abundance of beneficial microorganisms and improving the production of short-chain fatty acids. Arabinoxylan (AX) is a major component of most dietary fibers and has been shown to exhibit potential prebiotic properties and modulate gut microbiome composition. This study aimed to investigate the in vitro impact of bioengineered wheat arabinoxylan on depression-inversely linked gut microbes and human gut microbiome diversity and metabolism. This study demonstrates the ability of bioengineered AX to stimulate the growth of depression-inversely linked gut bacterial species (Faecalibacterium prausnitzii and Lacticaseibacillus rhamnosus LGG). On the microbiome composition, the bioengineered AX induced an increased abundance of beneficial bacterial taxa (Bacteroides, Bifidobacterium, Anaerofustis, and Eubacterium) compared to the control and native AX. These effects on microbes translated into significant metabolic activity and produced primary SCFAs (acetate, butyrate, and propionate). The findings from this study suggest that bioengineered wheat arabinoxylan could be considered a promising strategy for fostering next-generation prebiotics targeting depression-inversely linked gut microbes and also supports the structure-function relationship between AX and the human gut microbiome.

Ekonomiska beslut tagna på magkänsla är ett av de fundamentala finansiella tillvägagångssätten.Beslut tagna på fel premisser kan leda till förluster. Genom att ta rätt beslut baserat på rätt premisser kan resultaten bli önskvärda. Det finns många teorier och förklaringsmodeller för att förklara beslutsfattande. Även om det är många teorier så är dessa uppdelade i huvudsak i två typer, normativ teori och deskriptiv teori. Den normativa stödjer rationellt beslutsfattande, den senare hur besluten tas av människor. Både dessa teorier speglar verkligheten, även beskrivande teori söker en viss nivå av rationalitet i det faktiska beslutsfattandet.  Studien utfördes med en kvalitativ metod, där underlaget baserats på intervjuer av sju beslutsfattare som tar någon form av finansiella beslut. Analysen av denna undersökning visade att magkänsla är något de undersökta respondenterna använt sig av vid beslut, ibland godtycklig och ibland med en stark underliggande bas av rationellt tänkande.  Uppsatsen kan visa att magkänsla enligt teorins begrepp är varierbar beroende på kunskapsområde. I stället går det att understryka att den används vid en mängd olika situationer. Slutsatsen visade att det är alltför många definitioner, distinktioner och grundläggande förutsättningar som var tvunget att redas ut först innan frågan kunde besvaras i sin helhet, då fråganinte gick att besvara på ett rimligt kortfattat sätt under tio veckor. Undersökningen visade att magkänsla och finansiellt beslutsfattandet trots det används enligt teorin och i denna undersökning. / Financial decisions made on gut feeling are one of the fundamental financial approaches. Decisions made on the wrong premises can lead to financial losses. By making the right decision based on the right premises, the results can be desirable. There are many theories and models to explain decision making. Although there are many theories, these are mainly divided into two types, normative theory and descriptive theory. The normative supports rational decision-making, the latter how people make decisions. Both of these theories reflect reality, even descriptive theory seeks a certain level of rationality in actual decision-making. The study was carried out using a qualitative method, where the data was based on interviews with seven decision-makers who make some form of financial decision. The analysis of this survey showed that gut feeling is something the surveyed respondents used in decisions, sometimes arbitrary and sometimes with a strong underlying basis of rational thinking. The essay can show that gut feeling according to the concept of the theory is variable depending on the area of knowledge. Instead, it can be emphasized that it is used in a variety of situations.The conclusion showed that there are too many definitions, distinctions and basic conditions that had to be sorted out first before the question could be answered in its entirety, as the question could not be answered in a reasonably concise manner for ten weeks. The study showed that gut feeling and financial decision making are nevertheless used according to the theory and in this study.

The gut microbiota plays a major part in maintaining the health of a human host. Countless of crucial functions in the body, including immune responses, cell signaling and energy metabolism to name a few, are conducted by the gut microbiota and its metabolites. Accordingly, it is of interest to gain knowledge on what can alter the gut microbiota, as these alterations by extension can give rise to adverse health effects. In this study, the impact of polychlorinated biphenyl (PCB)- and organochlorine pesticide (OCP) exposure on tricarboxylic acid (TCA) cycle metabolites, short-chain fatty acids (SCFAs) and bile acids, as well as other polar and semi-polar metabolites, which are all related to the gut microbiota, were investigated. An in vitro fermentation of faecal samples exposed to a PCB/OCP mixture was performed, and liquid chromatography-time of flight mass spectrometry (LC-qToF-MS) targeted and non-targeted approaches were applied to the extracts. The results obtained suggested that PCBs and OCPs most likely have an effect on the levels of several features of the gut metabolome with either increased or decreased levels upon exposure. Bile acids and TCA metabolites appear to follow a trend of decreasing levels, while no apparent effects could be seen for the SCFAs. Furthermore, distinct concentrations of the PCB/OCP mixture appear to induce different changes in gut microbiota functioning, which highlights the importance of performing dose-response studies when exploring biological effects of these compounds. The identification of different metabolite profiles during fermentation also allows for the possibility of further investigation of potential biomarkers to assess PCB/OCP exposure.

PURPOSE OF REVIEW: This review article aims to explore the GI changes induced by SARS-CoV-2 and how gut microbial homeostasis can influence these changes and affect the lung-gut axis and its relationship with the induction of the cytokine release syndrome in severe COVID-19 patients. RECENT FINDINGS: Coronavirus disease 2019 (COVID-19) affects not only the respiratory system but can produce multi-systemic damage. The expression of angiotensin-converting enzyme 2 (ACE-2) receptors in the gastrointestinal (GI) tract, the high prevalence of GI symptoms in severely ill COVID-19 patients, and the abnormalities described in the gut microbiome in these patients have raised concerns about the influence of GI tract as a risk factor or as a potential modulator to reduce the severity of COVID-19. Understanding the mechanisms by which gut dysbiosis may influence viral transmission and disease progression in COVID-19 may help in shaping how accessible therapies, like diet modulation, can potentially help beat the devastating consequences of COVID-19.