Microbial trimethylamine-N-oxide as a disease marker: something fishy?

Production of trimethylamine-N-oxide (TMAO) via the gut microbiota has recently been proposed as an important pathophysiological mechanism linking ingestion of 'unhealthy foods', such as beef (containing carnitine) and eggs (containing choline), and the development of atherosclerosis. Hence, TMAO has gained attention as a novel biomarker for cardiovascular disease. However, fish and seafood contain considerable amounts of TMAO and are generally accepted as cardioprotective: a puzzling paradox that seems to have been neglected. We suspect that the TMAO story may be a red herring.

Probiotic lactic acid bacteria - the fledgling cuckoos of the gut?

It is tempting to look at bacteria from our human egocentric point of view and label them as either 'good' or 'bad'. However, a microbial society has its own system of government - 'microcracy' - and its own rules of play. Lactic acid bacteria are often referred to as representatives of the good ones, and there is little doubt that those belonging to the normal intestinal flora are beneficial for human health. But we should stop thinking of lactic acid bacteria as always being 'friendly' - they may instead behave like fledgling cuckoos.

Indole - the scent of a healthy 'inner soil'.

Tryptophan is an essential amino acid with an indole nucleus. Humans cannot produce this amino acid themselves, but must obtain it through their diet. Much attention is currently paid to the wide physiological and clinical implications of the tryptophan-derived substances, serotonin and kynurenines, generated by human enzymes following the intestinal absorption of tryptophan. However, even before being absorbed, several microbial metabolites of tryptophan are formed, mainly from 'malabsorbed' (incompletely digested) proteins within the colon. The normal smell of human faeces is largely due to indole, one of the major metabolites. Recent studies indicate that this foul-smelling substance is also of utmost importance for our health.

Wax esters from the marine copepod Calanus finmarchicus reduce diet-induced obesity and obesity-related metabolic disorders in mice.

We showed previously that dietary supplementation with oil from the marine zooplankton Calanus finmarchicus (Calanus oil) attenuates obesity, inflammation, and glucose intolerance in mice. More than 80% of Calanus oil consists of wax esters, i.e., long-chain fatty alcohols linked to long-chain fatty acids. In the present study, we compared the metabolic effects of Calanus oil-derived wax esters (WE) with those of purified eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) ethyl esters (E/D) in a mouse model of diet-induced obesity. C57BL/6J mice received a high-fat diet (HFD; 45% energy from fat). After 7 wk, the diet was supplemented with either 1% (wt:wt) WE or 0.2% (wt:wt) E/D. The amount of EPA + DHA in the E/D diet was matched to the total amount of n-3 (ω-3) polyunsaturated fatty acids (PUFAs) in the WE diet. A third group was given an unsupplemented HFD throughout the entire 27-wk feeding period. WE reduced body weight gain, abdominal fat, and liver triacylglycerol by 21%, 34%, and 52%, respectively, and significantly improved glucose tolerance and aerobic capacity. In abdominal fat depots, WE reduced macrophage infiltration by 74% and downregulated expression of proinflammatory genes (tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1), whereas adiponectin expression was significantly upregulated. By comparison, E/D primarily suppressed the expression of proinflammatory genes but had less influence on glucose tolerance than WE. E/D affected obesity parameters, aerobic capacity, or adiponectin expression by <10%. These results show that the wax ester component of Calanus oil can account for the biologic effects shown previously for the crude oil. However, these effects cannot exclusively be ascribed to the content of n-3 PUFAs in the wax ester fraction.

Oil from the marine zooplankton Calanus finmarchicus improves the cardiometabolic phenotype of diet-induced obese mice.

The aim of the present study was to investigate the effects of oil extracted from the zooplankton Calanus finmarchicus (Calanus oil) on diet-induced obesity and obesity-related disorders in mice. C57BL/6J mice fed a high-fat diet (HFD, 45% energy from fat) exhibited increased body weight and abdominal fat accumulation as well as impaired glucose tolerance compared with mice fed a normal chow diet (10% energy from fat). Supplementing the HFD with 1.5% (w/w) Calanus oil reduced body-weight gain, abdominal fat accumulation and hepatic steatosis by 16, 27 and 41%, respectively, and improved glucose tolerance by 16%. Calanus oil supplementation reduced adipocyte size and increased the mRNA expression of adiponectin in adipose tissue. It also reduced macrophage infiltration by more than 70%, accompanied by reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6 and monocyte chemotactic protein-1). The effects of Calanus oil were not only preventive, but also therapeutic, as the oil proved to be beneficial, regardless of whether the supplementation was started before or after the onset of obesity and glucose intolerance. Although the present study cannot pinpoint the active component(s) of the oil, there is reason to believe that the n-3 fatty acids EPA and DHA and/or antioxidants are responsible for its beneficial effects. It should be noted that the concentration of n-3 fatty acids in the Calanus oil diet was considerably lower than the concentrations used in similar studies reporting beneficial effects on obesity and obesity-related abnormalities.

[Mobilization of mesenchymal infection defense]. / Mobilisering av det mesenkymale infeksjonsforsvar.

BACKGROUND: Most infections are arrested in epithelial and superficial connective tissues long before antibodies and antigen specific killer cells have been induced; i.e. before the specific defence system has had time enough to come to the rescue. Microbial substances that activate and modulate this non-specific first-line defence in and near the body surfaces may enhance disease resistance, mainly by stimulating the production of anti-microbial substances by epithelia and by local activation of tissue macrophages. MATERIAL AND METHODS: There are many different microbial substances that can activate macrophages. Beta-1,3-glucans from yeast and mushrooms are the most obvious candidates for pharmaceutical development because their chemical composition and mode of action has been clarified in great detail. RESULTS: Beta-1,3-glucans in purified form provide efficient protection of animals against infections by virus, bacteria, fungi and parasites. Such enhanced protection is obtained after injection as well as after oral or mucosal administration. Beta-1,3-glucans also counteract the toxic effects of bacterial endotoxins and enhance the body's capacity to destroy cancer cells. INTERPRETATION: Activation of non-specific immunity in epithelia and in connective tissues by purified microbial substances corresponds to early events in a natural infection process and renders animals more resistant to infections. This way to enhance resistance to microbial infections has been applied with success in animal husbandry with beta-1,3-glucans administrated orally or onto mucosal surfaces. Corresponding use in human medicine is a realistic possibility, in addition to the use of microbial immune modulators as adjuvants in mucosal vaccines.